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| 1 | Pharmacokinetics
| Rubio et al.
| 2021
| Chromatographic-mass spectrometric analysis of the urinary metabolite profile of chlorphenesin observed after dermal application of chlorphenesin-containing sunscreen | Open-label bioequivalence study | 8 | NR | NR
| CPH | Oral | 250 mg | Single dose | | NR
| NR
|
| 2 | Pharmacokinetics | Zou et al.
| 2008
| Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study
| Crossover randomized open-label bioequivalence study | 24
| 23.5 (22-30) | Healthy males
| CPH | Oral
(capsules vs tablets) | 200 mg after 12h overnight fast | Single dose 1 week washout | After oral administration, CPH is absorbed from the GI tract and hydrolyzed into chlorophenoxyacetic acid. As a prodrug, CPH is not detected in plasma. Pharmacokinetic properties of chlorophenoxyacetic after 2 oral formulations of generic CPH hydrochloride administration: Cmax of the test and reference formulation: 12.6±2.8 and 12.8±3.0 μg/mL, respectively. Tmax of the test and reference formulation: 2.1±0.4 and 2.0±0.3 h. T1/2 of the test and reference formulation: 5.8±2.7 and 6.0±2.1 h. AUC 0-24 of the test and reference formulations: 34.1±7.9 and 34.2±8.1 μg/mL/h.
Compared with the reference tablet formulation, the CPH hydrochloride capsule (test) formulation had no statistically significant differences in bioavailability (p>0.05; Power =0.99) and no period or sequence effects were observed for any pharmacokinetic property.
| CPH hydrochloride was well tolerated by all the volunteers. No AEs were reported by subjects or found on analysis of vital signs or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis). AEs associated with CPH hydrochloride (eg, excitement, insomnia, lassitude, headache) were not reported during the study or 1 week after the study.
| The authors would like to thank JianMa Pharmaceutical Corporation for providing the capsule formulation of CPH hydrochloride, including the 4-chlorophenoxyacetic acid and CPH hydrochloride reference standards used in this research |
| 3 | Psychiatry & psychology | Popa et al.
| 1994
| Antagonic-stress superiority versus meclofenoxate in gerontopsychiatry (alzheimer type dementia)
| Parallel DB-randomized comparative trial | 63 CPH: 31
Antagonic- Stress: 32
| | Elderly with mild to moderate senile dementia
| CPH (Sintofarm, Bucharest, Romania) | Oral
(capsules:
2 gastrosoluble and 1 enterosoluble with lactose) | 1560 mg/day
(260 mg x2=520 mg, before each meal) "A total MF dose of 1520 mg/day" (mistake)
| 3 months | Degrees of improvements (reduction of geriatric psychopathology and recovery of cognitive functions) were significant in both treatments (final vs. baselines): for AS p<0.001 and for MF from p<0.01 to 0.001, indicating the utility of these neurometabolic nootropics in prolonged treatment of senile dementia of Alzheimer type. Final comparisons between treatments evidenced the superiority of AS vs. MF on SCAG (Sandoz Clinical Assessment-Geriatric) and SASG (Self-Assessment Scale-Geriatric) (p<0.05, 0.01 or 0.001). The intensity of geriatric psychopathology assessed by SCAG (1 severity interval=18) was reduced in total score, from the superior limit of mild to moderate (72 - 54 level) to mild (54 - 36 interval), by AS from 71.2±7.7 to 46.1±6.5 (-35.3%) vs. MF from 68.3±7.2 to 52.0±7.6 (-23.9%).
The reductions of the scores in SCAG I-V subscales listed were:
AS (from pre to post) vs. MF (from pre to post) Cognitive dysfunction: -32.7% (from 15.3±2.5 to 10.3±1.9) vs. -26.1% (15.3±1.9 to 11.3±2.6)
Interpersonal relationships: -38.7% (from 16.8±3.2 to 10.3±2.0) vs. -23.3% (15.9±2.3 to 12.2±2.5)
Affective disorders: -40% (from 14.0±2.1 to 8.4±1.5) vs. -28.4% (12.7±2.3 to 9.1±1.6)
Apathy: -26.7% (from 13.1±2.7 to 9.6±1.7) vs. -18.5% (13.0±1.9 to 10.6±2.0)
Somatic dysfunction: -37% (from 11.9±1.8 to 7.5±1.3) vs. -23% (11.3±2.3 to 8.7±1.9)
Symptom frequency autoevaluated by SASG (same variables as SCAG) also decreased, from the superior limit of mild to moderate to mild interval, by AS with 21.1 (-30.9%) vs. MF with 14.1 (-20.9%). The reductions of the scores in SASG I-V subscales were:
AS (from pre to post) vs. MF (from pre to post) Cognitive dysfunction: -29.3% (from 15.7±2.5 to 11.1±2.0) vs. -23.7%(15.2±3.0 to 11.6±2.8)
Interpersonal relationships: -34.6% (from 16.2±3.3 to 10.6±2.1) vs. -18.9% (14.8±2.0 to 12.0±2.1)
Affective disorders: -34.7% (from 12.1±2.3 to 7.9±1.6) vs. -24.4% (13.1±2.3 to 9.9±2.0) Apathy: -22.2% (from 13.5±2.6 to 10.5±1.7) vs. -17.2% (12.8±2.4 to 10.6±2.2)
Somatic dysfunction: -34.5% (from 11.0±2.4 to 7.2±0.9) vs. -20% (11.5±2.5 to 9.2±2.1)
Recovery by nootropic treatments of attention-concentration evaluated by digit symbol increased 53.3% (from 7.5±1.6 to 11.5±2.4) by AS treatment (from weak baseline to medium final level) and 19.5% (from 8.2±1.4 to 9.8±1.6) by MF treatment (from medium baseline to medium final interval), meaning a more than 2.5-fold larger improvement by AS than by MF. Memory-learning restoration assessed by WMS (MQ) increased by 33.6% (from 81.3±9.8 to 108.6±11.4) in case of AS treatment (from the inferior limit of mild deficit, 81-90, to the upper level of medium memory, 91-110) and 22.1% (from 82.0±6.5 to 100.1±11.3) in case of MF treatment (from the inferior limit of mild deficit, up to the middle level of medium memory). The cognitive performance (general intelligence) evaluated by IQ of WAIS also improved by the two nootropica: the verbal, the performance, and the full IQ values increased by 16.8% (from 99.5±11.3 to 116.2±11.5), 26.4% (from 87.8±7.9 to 111.0±13.5) and 22.8% (from 93.0±8.4 to 114.2±11.9), respectively, in the AS treated groups, whereas the same improvements amounted to 9.1% (from 100.2±10.6 to 109.3±12.3), 10% (from 93.0±10.0 to 102.3±14.5) and 8% (from 97.1±7.9 to 104.9±12.6) in the MF treated patients. Again in this test AS was more efficient than the MF alone: more than 2.5-fold in the performance IQ and more than 2-7-fold in the full IQ. Accordingly, restoration of cognitive performance was also detected as shown by a reduction of the WAIS deterioration index by 56.5% (from 15.4±4.3 to 6.7±3.9) and 29% (from 13.8±4.4 to 9.8±4.1) in the AS and MF groups, respectively. Both nootropic a reduced mental impairment from the 19-10% range (possible deterioration) to the 9-0% level (nonsignificant impairment, or physiological deterioration), but the efficacy was more than 2.2 times higher with AS than with MF treatment.
| Toxicity in our treated groups was very low. CPH can be applied up to a dose of 24 g/day i.v. or 10 g/day oral in anoxic syndromes, in severe barbiturate intoxications or in traumatic comas with serious disorders of consciousness. Note: These doses are extremely high in comparison to the doses used in the rest of the clinical trials. We believe they are likely an error, especially the i.v. dose, which is higher than the oral dose.
| NR
|
| 4 | Neurological symptoms | Stoica & Enulescu | 1991
| Correction by centrophenoxine of abnormal catecholamine response to postural stimulus in patients with orthostatic hypotension due to brainstem ischemia (abstract only) | Open-label
| 25
| NR
| Patients with orthostatic hypotension due to brainstem ischemia
| CPH | NR | 800 mg/day | 10 days | Before therapy, the patients responded to posture by a depression in norepinephrine excretion and a rise in epinephrine excretion. After treatment, patients responded to posture like normals, i.e. by a rise in norepinephrine excretion and a reduction in epinephrine excretion. Although the orthostatic blood pressure fall was less marked after treatment, the favorable clinical effect of the drug could not be correlated significantly with the restoration of catecholamine response to posture after treatment.
| NR
| NR
|
| 5 | Metabolism & biochemistry | Fülöp et al.
| 1990
| Effects of centrophenoxine on body composition and some biochemical parameters of demented elderly people as revealed in a double-blind clinical trial | DB-RCT
| 50 (25 male/25 female) 25 CPH group 25 control group
| 77.9 (treatment) 77.4 (placebo)
| Residents from a nursing home with medium level dementia
| Helfergin (Promonta, Hamburg, F.R.G.) | Oral
(tablets) | 2 g/day
(500 mg x2 after breakfast, 500 mg x2 after lunch) | 8 weeks (following 2-week run-in with placebo) | This trial has the same study population than trial #7 (Pek et al., 1989). Body composition Placebo group: no significant changes occurred in either males or females. The only exception is the intracellular fluid volume (ICV) of females, which displayed a significant increase. Treatment group: significant changes in various parameters:
The males displayed a decrease in their extracellular fluid volume (ECV), and also in interstitial fluid volume (ISV; although this latter did not reach the significance level), whereas the female treatment group showed more changes: practically all parameters except bodyweight and ISV showed a significant increase (total body water, ICV, exchangeable K+ and lean body mass) or decrease (ECV, ISV, total blood volume, plasma volume, red cell mass, exchangeable Na+ and total body fat).
A significant increase in the average intracellular water content (2.2-2.5% by weight) in the treatment group. CPH treatment significantly increased the intracellular water content of both male and female patients (from 64.9±3.1 to 67.1±2.4 in males and from 64.5±3.1 to 67.1±1.2 in females; 3.4% and 4.0%, respectively; mean increase of 3.7%), whereas the placebo group displayed no change (from 66.2±1.6 to 66.1±0.7 in males and from 66.9±1.7 to 67.3±1.8 in females; -0.2% and 0.6%; mean increase of 0.2%).
Serum lipid composition did not change considerably in either group during the experimental period, although some marginal changes were found. HDL-C increased in male placebo groups, whereas TG decreased in female placebo experiments. The treatment group did not reveal any significant influence on either of the sexes. Although some statistically significant changes in hormone levels can be seen between the data before and after the treatment in both groups and sexes, the fact that most of the differences occurred in both groups may indicate that the alterations are more of a seasonal or psychological origin, than true effects of CPH (i.e. increase in T4 and TSH).
The rehydration of the intracellular mass caused by the CPH treatment may have a positive influence on various body functions. We also demonstrated an improvement in psychometric tests (Pék et al., 1989).
All significant changes: body composition hormonal changes significant decreases were reported in one or both genders, in both grps, in: ↑T4 was observed in all but control grp males ↓ACTH was observed in control grp (F)†† ↓COR in CPH grp males; CPH grp females had a non-significant change of approximately equal magnitude in the same direction
outliers were sometimes excluded from the analysis of hormonal changes lipids were also measured, and did not change significantly in the CPH grp, however: ↓TG in control females ↓HDL-C in control males
starting mean body weight was 66.7 kg (males) 57.1 kg (females) and remained "practically invariate" at the end of the trial
† males of the same grp had a non-significant change of approximately equal magnitude in the opposite direction
†† males of the same grp had a non-significant change of approximately equal magnitude in the same direction
| Three dropouts from the verum group (illness followed by death) occurred during the treatment period (described in Pék et al., 1989) Additionally, one case more in the female verum group after treatment, since the 73-year-old patient No. 49 refused to perform the psychometric tests after treatment, although she performed the blood tests described here. The 61-year-old patient No. 15 refused to perform the blood tests after the trial for personal reasons (afraid of the repeated blood-taking intervention). However, he did finish the entire treatment period and also performed the psychometric tests. no dropouts from control grp The dropouts were not considered related to treatment by the authors
| NR
|
| 6 | Sleep & consciousness | Kinoshita
| 1990
| Quantitative pharmaco-EEG study of nootropics (abstract only) | Comparative
| NR
| NR
| Healthy young volunteers
| CPH | NR | NR | Single dose | EEG changes induced by these substances in normal subjects were an increase in alpha activity, particularly in higher frequency range above 9.5 Hz, and an associated decrease in slow activity and fast activity, which are different from those of the other psychotropic drugs. In the physiological aging process, alpha activity gradually decreases. The EEG changes induced by nootropics are the reverse of this process, suggesting the antagonistic efficacy in the geriatric changes.
| NR
| NR
|
| 7 | Psychiatry & psychology | Pék et al.
| 1989 | Gerontopsychological studies using NAI ('Nürnberger Alters-Inventar') on patients with organic psychosyndrome (DSM III, Category 1) treated with centrophenoxine in a double blind, comparative, randomized clinical trial | DB-RCT
| 50 (25 male/25 female) | 77.3 (treatment) 77.4 (placebo)
| Residents from an old age home with medium level dementia | Helfergin (Promonta, Hamburg, F.R.G.) | Oral
(tablets) | 2 g/day
(500 mg x2 after breakfast, 500 mg x2 after lunch) | 8 weeks | Psychometric tests and behavior: Placebo treatment induced an improvement in 28% of the cases (7 out of 25 patients). The percentage of improved cases in the treatment group was 47.6% (10 out of 21). "Although our method of evaluation cannot be considered as a rigorously acceptable mathematical approach, this difference can be considered as significant".
However, our calculation from the participant-level data shows a negative effect of CPH on test II, which assess mental performance. CPH group had a negative score, while the placebo showed no effect (-19.4% vs. +3.4%; p=0.03). The average change per memory test/person was only +9.0% in the placebo group, i.e., just slightly above the assumed ±5% scatter, whereas it was +21.2% in the treatment group. However, our calculations revealed that there was no significant difference (p=0.1492).
In the placebo groups, 28.6% of the improved patients (2/7) showed really an improved health status according to the rating of the medical doctor, whereas in the treatment group 90% of the improved patients (9/10) obtained a + judgment from the doctors. Our calculation from the participant-level data shows a positive impact of CPH on test V, which assess daily life activities (placebo 6±12% vs CPH 8±14%; p=0.6871). The placebo effects observed in this trial are within the usual level (lower than 30%) which is simply due to the involvement of the patient in some new activity which represents a kind of psychological stimulation.
Worsened mental performance in the average score from all the test (final value): In the placebo group, only one patient (4%) fell in this group (Patient No. 3), and he was 85 years old. In the treatment group, five cases (23.8%) were of worsened status (average age: 79.4 years). This fact means that the CPH treatment with 2 g/day per person may represent a kind of metabolic load in some cases, especially for older patients.
The application of statistical methods to data obtained represents a serious difficulty for two reasons: (a) the patients fall in four groups (male and female, treatment and placebo, respectively), i.e., the number of cases per group is rather low; (b) in spite of the application of the inclusion and exclusion criteria listed before, there is considerable heterogeneity in the performance of the tested groups. This latter fact is explained partly by the age differences, nevertheless, it is also important that some of the values observed in the subtests do not fall in the standard ranges established by the NAI for practically healthy old persons. Therefore, the evaluation must have been based on the judgment of the intra-individual improvements or worsenings.
| Worsened mental performance:
In the placebo group, only one patient (4%) and he was 85 years old. In the treatment group, five cases (23.8%) with an average age of 79.4 years.
Three drop-outs occurred for intercurrent diseases + One partial drop-out: 8% of the participants Patient No. 19 (88-year-old, male, treatment group). During the second week of treatment, the patient complained about weakness, he could not walk, had no appetite. Temperature was normal. The treatment was interrupted and the randomization code opened: he belonged to the velum group. The weakness persisted for several days, and 2 weeks later, after lunch, he lost his consciousness, blood pressure dropped and the patient died within 20 min. Autopsy revealed circulatory insufficiency due to the failure of the left ventricle, pneumonia and arteriosclerosis. The death was attributed to senium and no signs were encountered indicating any connection of this case with the CPH treatment. Patient No. 21 (82-year-old, male, treatment group). This patient had a hypotonic syncope on the 9th day of treatment, his systolic blood pressure decreased to 110 mmHg. After this event he felt always very weak, remained in bed, the treatment was interrupted and the randomization code opened. He was from the treatment group. His status did not improve even thereafter, in spite of an intense antibiotic cure; pus and albumin was found in the urine. Proteus vulgaris infection was proven in the urine, 3 weeks later hematuria appeared, and the patient died the next day. The autopsy revealed pneumonia, prostate hyperplasia, erosions in the urinary bladder, as well as congestion in the liver and spleen. The death had no connection with the CPH treatment.
Patient No. 31 (84-year-old, female, treatment group). This patient suffered from Parkinson's disease, which, however, was well compensated by medical treatment, and she was willing very much to cooperate with us in the psychometric test. However, she started hallucinating on the 3rd day of treatment so that 2 days later we interrupted the CPH treatment (the randomization code was opened, she belonged to the treatment group). During the next 2 weeks her status was gradually deteriorating, at last she became cyanotic, and died, in spite of the treatment in the medical clinic. Autopsy: congestive pneumonia, general arteriosclerosis, pulmonary embolization, senium. No connection was found with the very short (5 days) CPH treatment.
Patient No. 49 (73-year-old, female, treatment group) refuted to perform the psychometric tests for some unknown reasons after having finished the complete treatment period. All three drop-outs described above had a very similar course as observed in the placebo group 6 weeks after the whole test was over: three female placebo-treated patients died within 10 days and the diagnoses were very similar. Congestive pneumonia, arteriosclerosis and senium appeared always with more or less expressed cardiac insufficiency.
| NR
|
| 8 | Movement disorders | Izumi et al.
| 1986 | Meclofenoxate therapy in tardive dyskinesia: a preliminary report | Open-label
| 12
| 50.5 (22-72)
| Psychiatric patients with abnormal involuntary movements induced by neuroleptics (dyskinesia)
| CPH | Oral | 600-1200 mg/day in three divided doses (600 mg for the first week, increased by 300 mg/day every week until 1200 mg) | 6-12 weeks | The 12 patients were 8 with persistent tardive dyskinesia, 1 with probable tardive dyskinesia and 2 with tardive dystonia; additionally, 1 patient with subacute oral dyskinesia. The ingestion of CPH led to a decrease in the scores for abnormal involuntary movement after 4 weeks of treatment in 7 of 11 patients (63.6%; p<0.02). An initial effect was observed at 2.6±0.4 weeks and the peak effect was observed after 6.9±1.1 weeks (n=7) of CPH treatment (mean±SE). A significant (p<0.02) reduction of the scores continued until the end of the 12-week drug study. The involuntary movements reappeared 4-8 weeks following the cessation of medication. The abnormal involuntary scale represented in figure 1 shows an average initial value of 38 to 21 after the 12 weeks of treatment, which is a reduction of 44.7% compared to pretreatment levels. Among the 11 with involuntary movements induced by chronically administered neuroleptics, 4 (36.4%) improved markedly, 1 (9.1%) moderately, 2 (18.2%) slightly, and there was no improvement in 4 (36.4%). Additionally, 1 patient with subacute oral dyskinesia, induced by administration of neuroleptics for 1 month, improved markedly. Three weeks after treatment, when she was getting 1200 mg/day, the oral dyskinesia disappeared completely. She continued to take the same dose of CPH for the next 3 months, when she displayed the signs of parkinsonism, with masked face, muscle rigidity, bradykinesia, loss of arm swing, and difficulty in speaking and tuming; all symptoms increased day-by-day. Approximately 1 month following withdrawal of CPH from the regular regimen, these parkinsonian signs and symptoms diminished, and involuntary movements have never reappeared.
| AEs such as excessive salivation, lacrimation, anorexia, diarrhea, hypotension, bronchospasm or aggravation of psychiatric symptoms never occurred. Case 7 was a senile patient who complained of intolerable side effects by the end of the sixth week when he was receiving 1000 mg CPH, and he refused further treatment. Case 8 lost weight by the end of the eighth week; we therefore stopped medication (1200 mg), but weight loss continued for several months thereafter. Laboratory data were normal. The nurses reported that this mentally retarded patient had trouble with other patients and was often seen trying to tear out his nails. Case 9 was our oldest patient, displayed dementia, and had a mild degree of iron deficiency anemia. In spite of ferrous sulfate administration (525 mg/day), the anemia was progressive. CPH (1200 mg) was stopped at the end of the eighth week, but the anemia did not improve. No malignancy was detected at that time. Case 12 developed signs of parkinsonism that diminished 1 month following withdrawal of CPH.
| NR
|
| 9 | Dementia & cognitive decline | Richter
| 1983 | Treatment results with Cerutil in age-related cerebral insufficiency in general medicine (abstract only) | Retrospective observational | 31
| NR
| Patients with cerebral insufficiency
| Cerutil
| Oral
| 1250 mg/day
| 8 weeks
| The results concerning the possibility of influencing clinical symptoms, the descriptions of complaints by the patients and the testing methods applied to allow the conclusion, that Cerutil can be regarded as a proven remedy, especially at the out-patient treatment of older people with cerebral insufficiency.
| | NR
|
| 10 | General | Wasilewski et al.
| 1981 | Comparative evaluation of psychoactive drugs used in patients with subacute and chronic cerebrovascular disorders (abstract only) | Randomized comparative trial
| 315
CPH: 41 Piracetam: 90 Piritinol: 107
Piriditol: 77
| 30-82
| Patients with cerebral circulatory disturbances | CPH | NR
| The best way of administration was giving the drugs in two doses in the morning hours and at noon | NR
| In the treated patients, improvement was achieved in a considerable proportion of cases (44-82%) treated with different drugs. This improvement manifested itself as regression or decreased intensity of neurotic complaints, labyrinthine-cerebellar signs, pyramidal signs, anxiety and fears, improvement of recent memory, attention, psychomotor activity. However, these benefits were not attributed to any of the specific trial drugs. The best results were obtained with Nootropil, moderately good with CPH, Encephabol, and poor with Piriditol.
| Drug tolerance was best with Encephabol, while that of other drugs was slightly worse. The only disquieting symptom was the activation of epileptic seizures in several patients treated with Nootropil or CPH.
| NR
|
| 11 | Metabolism & biochemistry | Schmid & Schlick | 1979 | Influence of centrophenoxin administered for one year in high dose on maximal oxygen consumption in aged persons (abstract only) | Open-label
| | 64 (treatment)
59 (control)
| NR
| CPH | NR
| 3 g/day
| 12 months
| A highly significant (2p<0.335) influence of the drug for increasing the maximum oxygen input has been found. The hypothesis is presented, that this effect is due to an increase in cardiac functional capacity. A significant decrease in fasting glucose levels has been found, while the glucose concentration one and two hours after administration of 100 grams of oral glucose have shown no significant changes. Bodyweight revealed a small but significant decrease.
| | NR
|
| 12 | Psychiatry & psychology | Marcer & Hopkins
| 1977 | The differential effects of meclofenoxate on memory loss in the elderly | DB-RCT
| 76 (44 males/32 females)
| 72.2 (treatment) 73.2 (placebo)
70.1 (control)
| Elderly subjects in good health (with intellectual deterioration due to aging)
| CPH | Oral
(tablets)
| 1200 mg/day (600 mg twice daily)
| 9 months
| Urine samples were taken at random intervals and analyzed for the presence of CPH. These showed that failure to take tablets was not a problem in this study. CPH appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering. However, there was no improvement in secondary memory function which required the retrieval, recognition or matching of material already assumed to be in store:
Immediate free-recall: there was no significant difference between active and placebo. The slight pre-treatment superiority of the placebo group being maintained throughout the trial.
Delayed free-recall: the superiority of the active group is highly significant (p<0.01) as is the treatment x session interaction (p<0.01). The interaction is due to the difference between the two groups not emerging until the second session. Treatment: from 63.4 (month 0) to 79.4 (month 3), to 66.1 (month 6), to 65.3 (month 9). Final change: 3% Placebo: from 63.4 (month 0) to 51.8 (month 3), to 55.8 (month 6), to 57.2 (month 9). Final change: -9.8%
Control: from 61.6 (month 0) to 64.4 (month 3), to 76.9 (month 6), to 67.1 (month 9). Final change: 8.9%
This control group consisted of patients who had a change of mind about taking the tablets. The reason they gave for this was that their health was already good, and they "didn't need to take anything").
Digit-span, recognition, past event and prose passage: there was no significant difference between the two treatment groups, nor was the interaction significant. Post-trial questionnaire: there was no significant difference between the two treatment groups for the health assessment. However, 67% of the active group reported that the tablets had had a beneficial effect compared with 42% of the placebo group (p<0.05). These subjects mentioned an improvement in conditions such as bronchitis, arthritis and other complaints associated with old age. Subjects who reported a beneficial effect of CPH consistently used terms like 'increased alertness' and 'feeling of well-being' to describe the change. The post-trial questionnaire data imply that the increase in memory function measured by the free-recall test was, in a number of cases, accompanied by an improvement in the carrying out of day-to-day activities.
| | We are indebted to Dr O. Morton and Dr A. Goldberg, research consultants to Reckitt and Colman Pharmaceutical Division, for their help in setting up the trial. We are also grateful to Reckitt and Colman for their generous financial support. |
| 13 | General | Herrschaft et al.
| 1974 | The effect of centrophenoxine on regional cerebral blood flow in man (in German) | Open-label
| 18
| 54.7
(range: 29-68) | Patients with cerebrovascular disease such as hemiparesis or hemihypesthesia
| CPH
| i.v.
| 1000 mg for 8 patients
500 mg for 8 patients
| Single dose
| The fast component of regional CBF, corresponding to blood flow in the gray matter: Administration of 1000 mg CPH caused an overall average increase after 15 minutes, of 9.2 mL/100 g·min (11.4%), in all 9 patients (100%) (p<0.05).
Reducing the dosage to 500 mg and measuring after five minutes failed to show any significant change in regional CBF (overall average change 2.5 mL/100 g·min or 3.5%). A slight increase in the fast component of blood flow was observed only in five of the nine cases (55.6%), while a slight decrease was observed in four patients (44.4%).
The slow component of regional CBF, corresponding to the white matter: remained unchanged at both dosages and measuring times (3.4% for the high dose and 2.8% for the half dose).
Total CBF increased significantly under the high dose (3.8-4.7 mL/100 g·min or 7.6-9.9%) and the increase was observed in 8 out of 9 (88.9%). Under half dose, only small changes were detectable.
The increase of the CBF in gray matter is interpreted as a secondary effect after the activation of CNS metabolism by CPH. | NR
| NR
|
| 14 | Psychiatry & psychology | Gedye et al.
| 1972 | A method for measuring mental performance in the elderly and its use in a pilot clinical trial of meclofenoxate in organic dementia (preliminary communication) | DB-RCT
| Initially, 28 (14 pairs) 12 (six pairs, all women) completed the tests (due to hospital discharge, illness or death from one of the pairs) Owing to death of a partner, two subjects were paired twice
| Median age of 80 (67-99) | Patients with mild to moderate degree of organic dementia | Lucidril | Oral
(tablets)
| 600 mg
| 6 weeks
| Control and CPH groups have similar pre-treatment median scores, which are close to the expected 50th percentile. The post-treatment scores differ quite markedly, the control group median decreasing by 20.2% (from 54.5 to 43.5) and the CPH group median increasing by 66.7% (from 52.5 to 87.5).
All CPH member of the pairs has done relatively better than the 'control' member of the pair (as seen in the pair difference). In four of the six pairs, the control member of the pair deteriorated while the CPH member of the pair improved. In one pair, both members improved but the CPH member more than the control. In one pair, both members deteriorated, but the control member deteriorated more than the CPH member.
| NR
| We are grateful to Dr O. Morton of Lloyds' Research Limited for his valuable advice and support in this project (Lucidril discovered by Lloyd Anphar Ltd.) |
| 15 | Psychiatry & psychology | Itoh et al.
| 1968 | Double-blind controlled trial of lucidril (meclofenoxate) in the post-traumatic syndrome, especially dizziness | Multicenter crossover DB-RCT
| Total 63 | 39±16 (18-90)
| Patients with post-traumatic syndrome (head injury sequelae) | Lucidril | Oral
(tablets) | 900 mg in three doses
| 4 weeks
(2 weeks on each arm) | Where only one showed improvement, it was taken to be the preference. This distinction was not made when both drugs showed about the same level of improvement. When the first drug was the trial one, its effect was considered to carry over to the second placebo, which actually has no effect. When the placebo came first, the possibility of the effect of order evoking improvement that continues into the real effect of the second drug was taken into account and the actual effectiveness was not demonstrable. Sequential Analysis of Dizziness: Lucidril is superior in 14 pairs, passing the upper limits [16 pairs in Table 6]. That is, given an alpha=5%, risk ratio, Lucidril shows a significant difference surpassing the placebo in the dizziness sequela of head injury; it is clearly effective. Preference by an effective order does not exist. Sequential Analysis of Headache: In this experiment Lucidril could not thereby be shown effective in headache.
Sequential Analysis of Nervous Instability and Irritability: The trial drug was preferential in 12 cases, slightly more than the placebo’s 8 cases. It fails to show a significant difference.
Sequential Analysis of Other Symptoms: tinnitus, memory disturbance, decreased spontaneity, lack of strength, and insomnia. As they do not inevitably occur in all subjects, there were not enough cases to display a significant difference. Likewise, in the weekly global judgment of psychiatric symptoms and social adaptation' there were many tied pairs and no significant difference.
Sequential Analysis of the Global Judgement at Test Completion: There were 36 untied and 15 tied pairs with 17 trial drug and 19 placebo preferences, which does not constitute a significant difference. No advantage in administration order could be found between the two drugs.
Lucidril, with improvement in 31 cases and ineffective in 15 (46 patients in total), was 67.5% effective. The placebo, with improvement in 26 cases and ineffective in 16 (42 patients in total), was 62% effective. Dividing by center: Lucidril, with improvement in 18 cases and ineffective in 11 (29 patients), was 62.1% effective while the placebo, with 12 improvement cases and 13 ineffective (25 patients), was 48% effective. Lucidril, with improvement in 13 cases and ineffective in 4 (17 patients), to be 76.5% effective and the placebo, with improvement in 14 cases and ineffective in 3 (17 patients), to be 82.3% effective.
Effect by age: Preference for the trial drug by age is generally striking in the 40-59-year group but gives somewhat poorer results at younger and older levels. In the EEG abnormal findings show a greater preference of the trial drug in dizziness, headache, and global judgment. However, when this data is subjected to sequential analysis, a significant difference of the trial drug over the placebo is found only for dizziness in the under 49 group.
| Of the total 63 subjects, 8 (~12.7%) experienced only mild disturbances: 2 thirst, 2 blurred vision, 1 nausea, 1 heartburn, 1 diarrhea and 1 insomnia. Since no abnormal changes were observed in the laboratory tests (blood, liver function, urine), blood pressure, and pulse, this information is omitted. Of a total 63 subjects, 51 completed the test and 12 dropped out: 7 after 1 week, 3 after 2 weeks, and 2 after 3 weeks. Since their clinic visits simply ceased, the reasons are unclear. Six of the dropouts had received the trial drug and the other 6 the placebo.
| NR
|
| 16 | Psychiatry & psychology | Oliver & Restell
| 1967 | Serial testing in assessing the effect of meclofenoxate on patients with memory defects | Crossover DB-RCT
| 28
| >60
| Patients with disturbances of memory and of intellectual
concentration.
"Mental confusional states, regardless of
aetiology" | CPH | Oral
(tablets) | 1200 mg/day (300x4)
| 9 weeks
6 weeks of treatment or placebo +
2 weeks washout | None of the group differences reached a significant level. In most of the tests, there were greater differences (although still not significant) between the pre-treatment and post-treatment scores, than between the CPH and dummy scores. Tests: Graylingwell Information Test for orientation in time and space, long-term memory and current information. Benton Visual Retention Test An arbitrary test of six questions on common information and simple calculations Digits forward and digits backward: administered and scored in the same way as the WMS Saying the alphabet within 30 secs Counting backward, from 20 to 1 within 30 secs and counting by 3, from 1 to 40, within 45 secs
The nursing observations were not strictly quantified; as many improvements and side effects were attributed to the dummy medication as to the active medication. These results show that in the group of patients tested, CPH did not improve memory or mental concentration as measured by any one of the tests. The test scores also fail to show any statistically significant improvement due to a non-specific placebo effect, or to learning.
Most of these patients were too confused to show marked placebo effects, and their memories were too poor for improvement due to learning to be significant. Many of the subjects had been confused or demented two years or more, and it is possible that if only acutely confused subjects had been taken, CPH might have had more effect than the dummy.
| No patient failed to take all the tests, except two (one almost blind, one with severe intention tremor) who were not included in the Benton Visual Retention Test (BVRT) series. The CPH tablets produced no unpleasant side-effects that were not also shared by the dummy medication.
| NR
|
| 17 | Psychiatry & psychology | Bower & McDonald
| 1966 | A controlled trial of A.N.P. 235 ("Lucidril") in senile dementia | Triple-blind RCT
| Total 32 (all females) | 76.5 (treatment) 76.9 (placebo)
| Patients with senile dementia
| Lucidril
| Oral
(capsule) | 800 mg/day (200x4)
| 12 weeks
| No significant improvement or deterioration was found in any of the 22 qualities studied from first to final ratings, nor in any of the intermediate ratings. Nurses rating scale (modified from the Barrabee-Hyde Hospital Social Adjustment Scale): appearance, eating, dressing, bathing and shaving, continence, sleep, daytime activity, verbal interaction, group participation, emotionality, interests and productivity.
Occupational therapy: attention span, performance, motivation, socialization. Psychiatrists rating scale: reality testing, emotionality. communication, manifest overt behavior, Intellectual functioning and aspirations.
It was concluded that the drug was of no obvious value in the treatment of senile dementia at the dosage administered and over the time period studied.
| | Lloyd Anphar Ltd., of London,
supplied the drugs and placebo tablets. |
| 18 | Perinatal & pediatric | Hu et al.
| 2008 | Phase III clinical trial of Xiaoer Yiniao Granule on children with enuresis of kidney-qi deficiency in comparing with meclofenoxate hydrochloride capsules (in Chinese) (additional information in Huang et al., 2011) | Multicenter DB-randomized comparative trial
| Initially: 480 From Cochrane data: 473 (although the sum from the groups is 446)
Full analysis set: 456
| 5-14
| Children with enuresis (of kidney‐qi deficiency) | CPH | Oral
(capsule) | 100 mg/day
30 minutes before bedtime
| 28 days
| In treating the syndrome of kidney‐qi deficiency of enuresis, the clinical cure rates, the markedly effective rates and the total effective rates in the two groups (TCM and CPH) were 26.33% (89/338) vs. 21.30% (23/108), 50.30% (170/338) vs. 50.00% (54/108) and 76.63% (259/338) vs. 71.30% (77/108), respectively. By non‐inferior test, the results suggested that the treatment group was non‐inferior to the control group in clinical curative effect. Improvements of Chinese medicine symptoms of two groups were as follows: cure rates, the markedly effective rates and the total effective rates were 20.71% vs. 16.67%, 41.42% vs. 37.04% and 62.13% vs. 53.71% respectively, there was no significant difference between the two groups (p>0.05). But there were significant differences between pretreatment and post-treatment in intragroup comparison on single symptoms, such as times of enuresis, depth of sleep and abnormal tongue and pulse display.
Xiaoer Yiniao granules in children enuresis of kidney‐qi deficiency was not only non‐inferior to the control group in clinical curative effect, but also had better safety.
| | NR
|
| 19 | Stroke | Lu et al.
| 2007 | The clinical efficacy of meclofenoxate hydrochloride in treatment of patients with acute intracerebral hemorrhage (abstract only) | RCT
| 266
| NR
| Patients with acute intracerebral hemorrhage | CPH | i.v. | CPH 0.25 g dissolved in 250 mL of 0.9% sodium chloride i.v. once a day | 14 days
| The improvement rates and scores of the NIHSS and GCS in the treatment group evaluated on days 7, 14 and 28 were significantly better than those in the control group (p<0.05). The total effective rates in the treatment group on days 7, 14, 28 were significantly higher than those in the control group (p<0.05).
CPH hydrochloride, which is effective and safe in the treatment of acute intracerebral hemorrhage, can improve the levels of neurological impairment and consciousness of the patients.
| | NR
|
| 20 | Psychiatry & psychology | Harris & Dowson
| 1986 | The effects of meclofenoxate on cognitive performance in elderly individuals with memory impairment: a placebo-controlled study
| Crossover DB-RCT
| 20 enrolled (8 females/1 male)
| 82.3
| Elderly individuals with impaired memory (mild to moderate Alzheimer's dementia)
| CPH | Oral
(tablets) | 1200 mg/day (600 mg twice/day)
| 34 weeks total: | Scores at the beginning of placebo and active period, at 6 weeks and at 12 weeks of administration of placebo and active were examined for significant differences between placebo and CPH. No significant differences between sets of scores could be shown:
| One resident died from a cerebrovascular accident and had been on placebo for 5 weeks prior to death. Three other residents died from bronchopneumonia during the trial; two of the three had been receiving CPH for the previous 6 weeks, while the other subject had received placebo for the preceding 8 weeks. Six residents were withdrawn; three of these had developed depressive symptoms (one receiving placebo and two receiving CPH at the time of withdrawal), one had difficulty taking tablets because of an oesophageal stricture and the other two subjects (one of whom was on placebo and one on CPH) were withdrawn because they had developed confusional states. Another resident did not complete the trial because she did not cooperate in the later part of the study.
| Reckitt Coleman Pharmaceutical Division provided supplies of meclofenoxate as Lucidril and placebo tablets. |
| 21 | Stroke | Cooperation Study Group on Acute Cerebrovascular Diseases | 1978 | Evaluation of the clinical efficacy of so-called brain metabolism activating agents on consciousness of acute cerebrovascular diseases -evaluation of meclofenoxate hydrochloride injection by a double-blind method- (abstract only) | Multicenter DB-RCT
| 82 39 with cerebral hemorrhage 23 with cerebral infarction 20 with subarachnoid hemorrhage
| NR
| Patients with acute cerebrovascular disease (within 3 weeks)
| Lucidril | i.v. | NR
| 8-10 days
| General improvement of CPH showed a tendency to be inferior to that of control on cerebral infarction, occlusion of the internal carotid (ICA) or the middle cerebral artery (MCA), and female with cerebral infarction (p<0.1). In improvement of consciousness, CPH was superior to control in patients of cerebral hemorrhage, but was inferior to control in patients of cerebral infarction in each period after administration of drugs. However, a possibility, that results obtained on cerebral infarction was due to uneven distribution in the severity between the patients of two groups on the day before administration of drugs, cannot be excluded, since there were more severe cases in the CPH group than control group.
full abstract: A multi-clinical, double-blind controlled study was carried out to evaluate the efficacy of meclofenoxate hydrochloride (Lucidril) injected intravenously on 82 cases with acute cerebrovascular diseases. Subjected diseases were cerebral hemorrhage (39 cases), cerebral infarction (23 cases), and subarachnoid hemorrhage (20 cases) within 3 weeks from onset. As a controlled drug, inert placebo (control) was used. Both drugs were administered for 8 to 10 days with basic therapy in each hospital. In this paper, the efficacy of meclofenoxate and control was statistically evaluated on general improvement and consciousness of acute cerebrovascular diseases, and the following results were obtained. (1). General improvement of meclofenoxate showed a tendency to be inferior to that of control on cerebral infarction, occlusion of ICA or MCA, and female with cerebral infarction (P<0.1). (2). In improvement of consciousness, meclofenoxate was superior to control on patients of cerebral hemorrhage, but was inferior to control on patients of cerebral infarction in each period after administration of drugs. However, a possibility, that results obtained on cerebral infarction was due to uneven distribution in the severity between the patients of two groups on the day before administration of drugs, can not be excluded, since there were more sever cases in meclofenoxate group than control group. | NR
| NR
|
| 22 | Stroke | Hasegawa et al.
| 1976 | The evaluation of clinical effects of Lucidril on the psychiatric symptoms of patients with cerebro-vascular disorder (abstract only) | DB-RCT
| 106 (40 males/66 females)
| >50
| Psychiatric patients with cerebrovascular disease
| Lucidril | Oral
(tablets) | 900 mg/day (300x3) | 4 weeks
| There were no significant differences between lucidril and placebo groups as to the global judgment, subjective symptoms and psychiatric evaluation. No significant differences were seen in the chronicity and types of cerebrovascular disorder between the two groups. When being evaluated as to the clinical symptoms, Iucidril showed some effectiveness on the early awakening and shoulder stiffness compared with placebo, although statistically not significant. There was no evidence that would indicate the effectiveness of lucidril on the psychiatric symptoms of patients with cerebrovascular disorder.
full abstract: Lucidril, cerebral metabolite-activator, has been widely used for the treatment of vertigo and dizziness, seen in the post- traumatic disorders. This study is to evaluate the therapeutic effects of lucidril on the psychiatric symptoms of patients with cerebro-vascular disorders. The subjects were 106 psychiatric patients (male: 40, female: 66) of age 50 and over who had been diagnosed as having cerebro-vascular disorders. The study was carried out on a double-blind basis and the effect compared with that of placebo. The subjects were given 3 tab. t.i.d. (lucidril 900 mg per day.) The effect of the drug was evaluated as to the subjective symptoms, psychiatric symptoms and global judgement after 4 weeks of medication, and comparison was made between lucidril and placebo groups. In addition, both subjective and psychiatric symptoms were evaluated before and 2 weeks after medication. The results: (1). In this study, there were no significant differences between lucidril and placebo groups as to the global judgement, subjective symptom and psychiatric evaluation. (2). No significant differences were seen as to the chronicity and types of cerebrovascular disorder between two groups. (3). When being evaluated as to the clinical symptoms, Iucidril showed some effectiveness on the early awakening and shoulder-stiffness compared with placebo, although statistically not significant. (4). As to the side action of the drug, 5 cases (9.4%) were seen in lucidril group and 3 cases (5.7%) in placebo-group. (5). As to the drop-out cases, there were 4 cases in the lucidril-group and 3 cases in the placebo-group. In conclusion, there was no evidence which would indicate the effectiveness of lucidril on the psychiatric symptoms of patients with cerebro-vascular disorder. |
| NR
|
| 23 | Dementia & cognitive decline | Vehreschild et al.
| 1975 | Long term treatment of involutional mental impairment with meclofenoxate: a double-blind trial (abstract only) | DB-RCT
| 62
| 45-75
| Patients "suffering from a weakness of cerebral capacity" [progressive reduction of mental performance with no clinically identifiable cause]
| Cerutil
| NR
| 600 mg/day
| 6-21 months on treatment
6-8 weeks on placebo
| Patients that could not be traced back to a clinically conceivable cause, were prescribed CPH; placebo was administered at different time points than CPH: 6-21 months CPH vs. 6-8 weeks placebo.
*It seems that there was a long-term single group report on CPH treatment (like case series), and a subset of patients took part in a DB placebo-controlled trial. Clinical EEG and psychometric examinations (d2 test) before and after treatment by Cerutil showed that in otherwise progressing illness no increase in symptoms was observed. The results prove that Cerutil may be recommended for long-term treatment in premature weakness of cerebral capacity.
full abstract: 62 patients aged from 45 to 75 yr suffering from a weakness of cerebral capacity that could not be traced back to a clinically conceivable cause, were prescribed 'Cerutil'. The medicament was administered over a period of 6 to 21 mth in a dosage of 600 mg/die. 28 of these patients received a placebo over a period of 6 to 8 wk as a double blind trial. Clinical electroencephalographic and psychometric examinations (d2 test) before and after treatment by Cerutil showed that in otherwise developing illness no increase in symptoms was observed. The results prove that Cerutil may be recommended for longterm treatment in premature weakness of cerebral capacity. | NR
| NR
|
| 24 | Psychiatry & psychology | Vojtechovsky et al.
| 1970 | The influence of centrophenoxine (lucidril) on learning and memory in alcoholics (abstract only) | | | NR
| Chronic abstaining alcoholics | CPH | Oral
| | | In comparison to placebo, only the Pauli test was sensitive to CPH treatment. A single dose of CPH significantly improved concentration (p<0.01) but did not affect sustained mental effort, arithmetic speed, word association rt, or recent memory in 10 chronic abstaining alcoholics.
In comparison to placebo (12 days before or after CPH therapy), 3 daily doses of 250 mg (750 mg) CPH for 12 consecutive days significantly improved the learning process (estimated by paired associates), short-term memory (by the Benton visual retention test) and memory quotient (by the Wechsler memory test) in 6 chronic alcoholics with marked memory disturbances (chronic korsakoff psychoses).
| NR
| NR
|
| 25 | Perinatal & pediatric | Wu
| 2010 | Clinical study of 100 cases of children with hypoxic-ischemic encephalopathy treated by meclofenoxate Injection (abstract only; in Chinese) | Randomized comparative trial
| 100 CPH, cerebrolysin and massage: 50
Control with breviscapine, cerebrolysin and massage therapy: 50
| NR
| Children with HIE | CPH | i.v. | NR
| NR
| In the treatment group: the systolic blood flow velocities in the anterior and middle cerebral arteries and basilar artery increased from 34.7±13.5, 43.8±11.2, and 35.5±14.5 cm/s to 48.8±12.3 (40.6%), 58.2±12.2 (32.9%), and 52.6±19.6 (48.2%) cm/s, respectively. In the control group: from 36.2±11.1, 42.8±13.5, 35.2±13.8 cm/s to 42.6±10.2 (17.7%), 50.2±11.8 (17.3%), 41.9±12.9 (19.0%) cm/s. The clinical total effective rate of the two groups was 90% (45/50) for the treatment group vs. 74% (37/50) for the control group. The CBF velocity changes and clinical symptoms in the treatment group improved compared with the control group (p<0.05). The efficacy of the CPH i.v. on the treatment of children with HIE is significant.
| NR
| NR
|
| 26 | Psychiatry & psychology | Pieschl et al.
| 1983 | Double-blind collaborative trial of centrophenoxine versus placebo for patients with neurasthenic syndromes (abstract only) (additional information in Table 3: Herrschaft Summary) | DB-RCT
| 52 in total
| 20-50
| "Outpatients with neurasthenic syndromes" | CPH | NR
| 2 g/day
| 4 weeks
| The results for the numerically largest group, consisting of 32 subjects with psycho-reactive neurotic disturbances (the other patients, not analyzed, had organic brain disturbances or endogenous psychoses), were evaluated statistically. Subjective evaluations, including the judgment of doctors as well as patients, indicated the significant superiority of drug treatment over placebo. A descriptive self-assessment and the d2 Test objectively and statistically corroborated the subjective findings. The HAWIE Numerical Repetition Test showed no significant difference between Ss treated with CPH and placebo.
| NR
| NR
|
| 27 | Stroke | Lu et al.
| 2006 | The efficacy of meclofenoxate hydrochloride in the treatment of acute cerebral infarction (abstract only) | RCT
| 198
| NR
| Patients with ACI (NIHSSs =8-22)
| CPH | i.v. | CPH 0.25 g dissolved in 250 mL of 0.9% sodium chloride i.v. | 14 days
| The NIHSS and the ADL scales at day 3, 7, 14 and 28 showed that the observer group and the control group had significant differences (p<0.05). CPH Hydrochloride is efficacious and safe in the treatment of ACI due to the improvement of neurological deficits and daily life activity of the patients.
| | NR
|
| 28 | Poisoning & anesthesia | Hou
| 2009 | The effect of meclofenoxate hydrochloride in the treatment of acute alcohol intoxication (abstract only) | Comparative trial
| 1716
CPH: 686
Naloxone control: 834
| NR
| Patients with acute alcohol intoxication | CPH | i.v. | NR
| Acute
| The age distribution and serum alcohol concentration of the two groups showed no significant difference by t-test (p>0.05). The clinical performance scores at admission were not significantly different by t-test. Clinical cure was achieved in both groups (improvement in motor coordination, intoxication symptoms, delirium and degree of impaired consciousness). CPH is comparable to naloxone in the clinical treatment of acute alcoholism.
| NR
| NR
|
| 29 | Perinatal & pediatric | Fang et al.
| 2010 | Meclofenoxate hydrochlor and hyperbaric oxygen (HBO) in the treatment of hypoxic-ischemic encephalopathy of newborn (abstract only; in Chinese) | RCT
| 120 CPH + HBO: 60
Control HBO: 60
| infant
| Full-term infants with HIE
| CPH | NR
| NR
| 10 days
| The effective rate (using NABA criteria before and after treatment) in the study group was significantly higher than that in the control group (p<0.01) ([NBNA] Neonatal behavioral neurological assessment). HBO combined with CPH is very effective in the treatment of infants with HIE, with less side effects.
| NR
| NR
|
| 30 | Stroke | Ji et al.
| 2007 | The effect of meclofenoxate hydrochloride on blood C-reactive protein in patients with acute cerebral infarction (abstract only) | RCT | 60
| NR
| Patients with ACI | CPH | i.v. | 300 mg/day
| 14 days
| Blood C-reactive protein concentrations and NIHSS sclae in the treatment group were significantly lower than that in the control group (p<0.01) and activities of daily living scales were significantly higher than that in the control group (p<0.01). CPH hydrochloride can lower the elevated blood CRP concentration in patients with ACI.
| NR
| NR
|
| 31 | Urinary
| Chen & Zheng
| 2010 | Urinary frequency, urgency, and incontinence associated with meclofenoxate (abstract only) | Case study
| 1 (female)
| 86
| Women with hypertension, sequelae of cerebral infarction, and hyperlipidemia | CPH | i.v. | CPH 0.25 g dissolved in 20 mL of sodium chloride 0.9% twice daily | Acute
| Patient receiving telmisartan, aspirin, nicergoline, simvastatin, Danhong i.v., and deproteinized hemoderivative of calf blood injection. After 14 days of therapy, Danhong and deproteinized hemoderivative of calf blood injection were stopped and an i.v. infusion of CPH was added to his regimen. On the day of CPH administration, the patient experienced urinary frequency, urgency, and incontinence. Renal function revealed a BUN (blood urea nitrogen) level of 7.10 mmol/L and a SCr (serum creatinine) level of 88 μmol/L. CPH was withdrawn immediately and other medications were continued, her symptoms relieved gradually. Three days later, her condition was stable and she was discharged.
| | NR
|
| 32 | Poisoning & anesthesia | Li
| 2009 | Clinical effect observation of meclofenoxate treatment for children with acute severe organophosphate poisoning (abstract only) | RCT
| 58
CPH: 30
Control: 28 with conventional therapy (inhaling O2, maintaining airway patency, gastric lavage, i.v. atropine and pralidoxime)
| NR
| Children with acute severe organophosphate poisoning | CPH | i.v.
| 120-200 mg/day (2x60-100 mg) | NR | 26/30 cases of the treatment group were cured (86.7%) and 19/28 cases of the control group (67.9% cure rate) (p<0.05). At the rescue of severe organophosphorus pesticide poisoning, the timely application of CPH can significantly improve survival rate, and deserve extensive use in clinic.
| NR | NR
|
| 33 | Poisoning & anesthesia | Zheng et al.
| 2011 | Effects and therapeutic analysis of meclofenoxate hydrochloride on the serum levels of SOD, GSH-PX and MDA in patients with acute carbon monoxide poisoning (abstract only) | RCT
| 72
| NR
| Patients with acute CO poisoning
| CPH | i.v. | 0.5 g/day
| 14 days | The serum level of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in the two groups had no significant differences before treatment (p>0.05). The serum level of SOD and GSH-PX in the two groups were significantly higher after treatment, but MDA was lower. After treatment, the serum level of SOD and GSH-PX in the treatment group was much higher than that in the control group. The serum level of MDA in the treatment group was much lower than that in the control group. The effective power of the treatment group was higher than that of the control group (vital signs and clinical symptoms?). CPH hydrochloride could obviously improve the clinic therapeutic effect of acute CO poisoning, eliminate oxygen free radical, inhibit lipid peroxidation, decrease the injury of brain cells by oxyradical and improve the prognosis.
| NR | NR
|
| 34 | Neurological symptoms | Chen
| 2007a | Efficacy of meclofenoxate in treating vertigo (abstract only) | Randomized comparative trial | 48
| NR
| Patients with vertigo
| CPH | i.v. | NR
| NR | | NR | NR
|
| 35 | TBI & coma | Bassem et al.
| 2018 | Safety and effectiveness of the use of Luciforte® 500 mg vial with patients admitted to the intensive care unit for impaired conscious level: a multi-center, retrospective, observational study | Multicenter, observational retrospective study | 300 (200 males/100 females)
| 55.7±16.5 | Patients (18-75) admitted to the ICU for CNS dysfunction due to:
| Luciforte | i.v.
| 1000 mg/day (500 mg twice daily)
| NR | There was a statistically significant improvement in the level of consciousness as measured by the GCS after treatment; p<0.001. The GCS increased by 23.3% (from 11.82±1.6 on ICU admission to 14.57±1.05 on discharge). This improvement was consistent regardless of the cause of disturbed conscious level, the underlying brain lesions, or the baseline APACHE II Score. Patients who showed improvement in GCS were 294 (98.0%) within a median period of 8 (I-Q range =6-10) days. GCS remained unchanged in only 6 patients (2.0%). No statistically significant difference was observed between patients who showed improvement and those who remained unchanged regarding any of their demographic or clinical characteristics, p>0.05.
| No AEs (serious or non-serious) were reported within the period of hospital stay. Luciforte® vials are a safe, well-tolerated drug.
| NR
|
| 36 | Dementia & cognitive decline | Fu et al.
| 2007 | Safety and efficacy of meclofenoxate in treatment of patients with vascular dementia (abstract only; in Chinese) | Open-label
| 56
| NR
| Patients with VaD
| CPH | NR
| 600 mg/day (0.2 g 3x a day) | 12 weeks | The results of the self-matched trial showed remarkable improvement in MMSE, CDR (clinical dementia rating) and ADL by 4.69, 0.82, 4.71 points respectively (p<0.01, 0.05 and 0.05) after treatment with CPH.
CPH is effective in treating patients with VaD. It can improve cognition and ability of daily life.
| 8 out of 56 patients (14.3%) showed mild side effects, such as dizziness, headache and nausea. CPH was well tolerated and safe.
| NR
|
| 37 | Psychiatry & psychology | Tang & Zhou | 2006 | A controlled study of meclofenoxate hydrochloride capsules combined with lithium carbonate in the treatment of depression (abstract only) | SB-RCT
| 69 | NR | Patients with depression | CPH | Oral
(capsule) | NR
| 6 weeks | After treatment, scores of the Hamilton Depression Scale (HAMD) in each week were significantly lower than those before treatment (p<0.01); at the end of the 2nd week, score-reducing rate of the HAMD was more in the control than in the research group (p<0.05) and there was no difference at the ends of 4th and 6th week. After treatment, there were no differences in effectual and effective rates between the 2 groups (p>0.05); the score of the Treatment Emergent Symptom Scale (TESS) were significantly lower in the research than in the control group (p<0.01). The efficacy of CPH hydrochloride capsules combined with lithium carbonate is equivalent to fluoxetine combined with lithium carbonate in the treatment of depression and the former has fewer side effects.
| | NR
|
| 38 | Dementia & cognitive decline | Zhang & Wang | 2007 | Clinical study of meclofenoxate hydrochloride in the treatment of vascular dementia Clinical study of meclofenoxate hydrochloride in the treatment of vascular dementia (in Chinese, but with additional info about AEs)
(abstract only) | Open-label
| 30 | NR | Patients with mild to moderate VaD | CPH | NR
| 600 mg/day (0.2 g 3x a day)
| 10 weeks | After treatment, the MMSE score improvement rate was 56.7% (17/30) and the CGI (clinical global impression) effective rate was 66.7% (20/30). Although the mean ADL reduction rate did not reach the effective improvement, most of the patients showed some improvement in their daily living ability.
CPH hydrochloride is an effective choice for the treatment of VaD.
| | NR
|
| 39 | TBI & coma | Umlauf et al.
| 1983 | The influence of centrophenoxine hydrochloride on SSEP in apallic patients (abstract only) | Open-label
| 10 (5 males/5 females) | 35 | Apallic head trauma patients in ICU
| CPH | i.v. | CPH 2 g dissolved in 250 mL laevulose daily | 14 days | In 8/10 (80%) patients, we saw a significant increase of the N20 amplitude in SSEPs (somatosensory evoked potentials are brain and spinal cord responses elicited by sensory stimuli) after 2 weeks of daily treatment. Parallel to this, the responsiveness to various external stimuli improved. This might be due to improvement of regional CBF or increased glucose utilization described elsewhere. Our results suggest that CPH hydrochloride could be a useful drug in the treatment of severe neurological deficits after head trauma.
| NR | NR
|
| 40 | Stroke | Lv & Huang
| 2008 | Meclofenoxate hydrochloride in patients with acute cerebral hemorrhage in the clinical efficacy observation (abstract only) | RCT
| 62 | NR | Patients with ACH
| CPH | NR
| NR
| 4 weeks | After 4 weeks of treatment, the neurological functional deficit scores were 33.3% lower in the treated group compared to the control group (9.6±6.3 vs. 14.4±7.6). There was a significant difference between the two groups (p<0.05). There were also significant differences between the two groups in terms of apparent effect rate (treated group 19/31 or 61.29%, control group 12/31 or 38.71%; p<0.05) and improvement rate (treated group 27/31 or 87.10% vs. control group 17/31 or 54.85%; p<0.05). Hydrochloric acid CPH can accelerate the recovery of neural function after cerebral hemorrhage.
| NR | NR
|
| 41 | Urinary | Zhu et al.
| 2003a | Meclofenoxate in treating urinary incontinence after acute cerebral infarction (abstract only) (additional information in Thomas et al., 2008) | CT | 80 (35 female, 45 males) | 63 | Patients with urinary incontinence after ACI
| CPH | Oral
| 900 mg/day (0.3 g x3 times a day)
| 4 weeks | The symptoms in the patients of the combined treatment group with or without aphasia and cognitive function were improved significantly (p<0.05, p<0.01, respectively), compared with those in the control group.
Incontinence: patients who did not improve, 9/40 CPH vs. 27/40 controls (p≤0.05) The MMSE improved significantly (p<0.01).
Unknown scale cognitive function: 34.5 CPH vs. 30.42 controls (p≤0.01) ADL (Barthel index) improved significantly, 37.4 CPH vs. 34 controls (p<0.01). CPH may play an important role in the improvement of cognitive function, ADL and MMSE of the patients with ACI. CPH is a safe and effective drug in treating urinary incontinence after ACI with less adverse reactions.
| | NR |
| 42 | Perinatal & pediatric | Teichmann & Schwebke
| 1973 | The performance of brain-organically impaired normal-intelligent children under Cerutil in a work trial (in German) | Crossover DB-RCT
| 18 | 10 | Pupils affected by cerebral-organic efficiency reductions (ADHD)
| Cerutil
(VEB Isis, Zwickau)
| Oral
| 200 mg/day for 7 days; 300 mg in the morning and 300 mg at noon every day for 11 days | 18 days | Children performed better in the second phase. 8 out of 9 children who received the placebo in the second phase (after drug administration phase) had better results with placebo, meaning that the drug is not strong enough to surpass the effect of learning by test repetition. In the placebo group, the average gain compared to before the test was 72 additions (12.8%). In the drug group, the average addition compared to before the test was only 9 (1.6%).
This is from an average total of 562 [589 according to our calculations] math problems initially completed to 634 in the placebo group and 571 in the CPH group =9.9% lower score on the Pauli test after CPH. The performance of children under the drug was lower than under the placebo. The drug had a performance-inhibiting effect in children with concentration disorders. During the test, the percentage of errors is low, but more errors were performed under the drug compared to the placebo (3.4% vs. 2%). The number of improvements did not increase under the drug. The performance curves for the CPH phase, over the approximately hour-long test, showed that participants' work rate tended to drop during the later part of the assessment Results from the survey: Parents who were aware of the existence of the placebo reported a better behavior under both, the drug and the placebo. However, the assessment did not find significant differences. Teachers aware of the placebo reported a deterioration in the discipline and the willingness of the class to learn decreased. However, no significant differences were observed in behavioral changes.
In summary, after Cerutil administration, a mean decrease in performance of 9.9% was observed in children due to a reduction in the purposeful (goal-directed) mental activity, as defined by the number of problems presented per unit of time in the Pauli test. Since the performance score is also reduced, there is a real deterioration in mental efficiency.
| | NR |
| 43 | Perinatal & pediatric | Zhang et al.
| 2021 | Clinical observation on 30 cases of enuresis in children with disharmony between heart and kidney type treated by self-made Qingxin Zhiyi Fang (abstract only) | Randomized comparative trial
| 60 | NR | Children with enuresis and disharmony between heart and kidney type | CPH | Oral
(capsule) | Once per day, which was taken at 0.5 hour before bedtime. Dose NR
| 4 weeks | Before treatment, the difference was not statistically significant in the scores of cardinal and assident symptoms between the 2 groups (p>0.05), and they were comparable. After treatment, the scores of cardinal and assident symptoms in the 2 groups significantly decreased, and the difference was statistically significant compared with those in the same group before treatment (p<0.05), moreover, the decrease in the treatment group was more significant (p<0.05). The total effective rate was 83.4% (25/30) in the control group and 93.4% (28/30) in the treatment group, and the difference was statistically significant between the 2 groups (p<0.05). The total effective rate of TCM syndrome score was 90% (27/30) in the treatment group and 80% (24/30) in the control group, and the difference was statistically significant between the 2 groups (p<0.05).
| NR
| NR |
| 44 | Pharmacokinetics
| Nan et al.
| 2021 | Bioequivalence study of meclofenoxate hydrochloride capsules by determination of dual active metabolites (abstract only) Determination of 2-dimethylaminoethanol in human plasma after oral meclofenoxate (abstract only) | Crossover comparative bioequivalence trial
| 21 | NR | Healthy subjects | CPH | Oral
(capsule) | 300 mg
| Single dose | The main pharmacokinetic parameters of the test capsule and reference capsule were as follows: For 4-CPA: Cmax: 27.4±4.2 and 26.2±4.3 mg/l (26.2 μg/mL)
AUC 0-t: 230.3±68.1 and 211.1±62.6 mg·h/L
AUC 0–∞: 238.9±71.7 and 219.0±65.8 mg·h/L
For DMAE: Cmax: 277.7±107.3 and 266.2±118.4 μg/l AUC 0-t: 721.1±172.7 and 736.0±216.9 μg·h/L
AUC 0–∞: 776.2±203.9 and 835.5±270.0 μg·h/L
The 90% CI of Cmax, AUC 0-t and AUC 0–∞ all fell within the equivalent range (80-125%). The two capsule preparations are bioequivalent. There are significant differences in the distribution and metabolism of 4-CPA and DMAE.
| NR
| NR |
| 45 | Stroke | Ma & Zhou | 2021 | Efficacy of combined cattle encephalon glycoside and ignotin and meclofenoxate in the treatment of acute cerebral hemorrhage and its influence on serum MMP-2/9,TSP-1/2,nerve-related factors and prognosis (abstract only) | RCT
| 123 | NR | Patients with ACH | CPH | NR | NR
| NR | The total effective rate in the observation combined group was higher (95.12%=39/41) than that in the control groups A (cattle encephalon glycoside and ignotin; 75.61%=31/41) and B (CPH; 78.05%=32/41) (p<0.05). After treatment, the volume of brain edema in the observation group was lower than that in the control groups A and B, the serum levels of MMP-2/9 (matrix metalloproteinase), TSP-1/2 (thrombospondin), NSE (neuron-specific enolase), NGF (nerve growth factor), and GFAP (glial fibrillary acidic protein) were lower than those in control groups A and B, and BDNF levels were higher than those in control groups A and B (p<0.05). The NIHSS and mRS of the observation group after treatment were lower than those of the control groups A and B (p<0.05). The combination of cattle encephalon glycoside and ignotin and CPH is effective in the treatment of ACH, which can reduce serum MMP-2/9 and TSP-1/2 levels, regulate nerve-related factors, promote the recovery of nerve function, and improve the prognosis.
| NR
| NR |
| 46 | Perinatal & pediatric | Yu et al.
| 2020 | Observation on the efficacy of a traditional Chinese pill in the treatment of pediatric enuresis (abstract only; in Chinese) | Randomized comparative trial
| 72 | NR
| Children with enuresis | CPH | Oral
(capsule) | NR
| NR
| The total efficiency of the observation group was higher than that of the control CPH group (p<0.05). After treatment, the TCM syndrome points of both groups were lower than those before treatment (p<0.05), and the observation group was lower than the control group (p<0.05). The recurrence rate in the observation group was lower than that in the control CPH group (p<0.05). The effect of the TCM Pill in the treatment of pediatric enuresis is better.
| NR
| NR |
| 47 | Perinatal & pediatric | Ma et al.
| 2020 | Clinical observation of 51 cases of pediatric enuresis with combined traditional Chinese and Western medicine in the treatment of lower yuan deficiency cold type (abstract only; in Chinese) | Randomized comparative trial | 102 | NR
| Children with enuresis | CPH | Oral
(capsule) | NR
| NR
| After treatment, the frequency of enuresis and arousal threshold of both groups decreased compared with those before treatment, and the observation group was significantly lower than the control group (p<0.05). The ADH level of children in both groups increased, and the observation group was significantly higher than the control group (p<0.05). The clinical treatment effect of the observation group was better, with an effective rate of 92.16% (47/51), which was significantly higher than the 74.51% (38/51) of the control group (p<0.05). The combination of Chinese and Western medicine is beneficial to improve bladder function, lower the arousal threshold and increase the concentration of ADH in the children's blood at night, which is worthy of clinical promotion.
| The observation group had higher safety, and the incidence of adverse reactions was 3.92%, which was lower than that of the control group (13.73%), and the difference was not statistically significant (p>0.05).
| NR |
| 48 | Perinatal & pediatric | Wang
| 2020 | Clinical effect of Mahuang decoction in the treatment of enuresis in children (abstract only) | Randomized comparative trial | 68 | NR
| Children with enuresis | CPH | NR
| NR
| NR
| After treatment, the number of enuresis, the scores of sleep-wake disorder and TCM syndrome in the two groups decreased, and those in the observation group were lower than the control CPH group (p<0.05). The total effective rate of treatment in the observation group was significantly higher than that in the control CPH group (p<0.05). Mahuang decoction has a significant clinical effect in the treatment of enuresis in children, it can significantly reduce the number of enuresis in children and improve the cure rate, which is worthy of clinical promotion and application.
| NR
| NR |
| 49 | Stroke | You | 2020 | Analysis of the efficacy of meclofenoxate in the treatment of acute cerebral hemorrhage (abstract only; in Chinese) | Retrospective observational trial
| 51 | NR
| Patients with ACH | CPH | NR
| NR
| 1 month
| After 1 month of treatment, the NIH Stroke Scale score decreased and the ADL score increased in both groups, and the NIHSS score in the observation group was lower than that in the control group, and the ADL score was higher than that in the control group, with statistically significant differences in both scales (p<0.05). The levels of C-reactive protein, TNF-α and IL-6 were reduced in both groups, and the observation group was lower than the control group; the differences were statistically significant (p<0.05). The treatment of ACH patients with CPH can effectively improve the level of inflammatory factors, promote the recovery of neurological function and improve the ability of self-care in daily life.
| NR
| NR |
| 50 | Stroke | Hou et al.
| 2019 | Efficacy of meclofenoxate combined with noninvasive intracranial pressure monitoring in treatment of acute cerebral hemorrhage and its effects on cerebral hematoma volume and inflammatory factors (abstract only) | RCT
| 124 | NR
| Patients with ACH | CPH | NR
| NR
| 1 month
| The total effective rate of the observation group was 87.10% (54/62), significantly higher than the 54.84% (34/62) of the control group (p<0.05). After treatment, the ADL score and MoCA score of the observation group were significantly higher than that of the control group, and the level of cerebral hematoma volume was significantly lower than that of the control group (p<0.05). After treatment, the levels of IL-6, TNF-α, high-sensitivity CRP and IL-1 in the observation group were significantly lower than those in the control group (p<0.05).
CPH combined with noninvasive intracranial pressure monitoring can significantly improve the clinical efficacy of patients with ACH, reduce inflammation, improve patients’ cognition, quality of life and daily living ability.
| | NR |
| 51 | Musculoskeletal | Li et al.
| 2019 | Effects of Kudiezi injection on diabetes patients complicated with cerebral infarction and bone mineral density (abstract only) | Randomized comparative trial
| 100 | NR
| Diabetes patients complicated with cerebral infarction
| CPH | i.v. | CPH 0.5 g dissolved in 250 mL of 0.9% NaCl
| 21 days
| There were no intra-group or inter-group differences between the clinical and biochemical indices of the two groups on the 21st day (p>0.05). The overall effective rate of the treatment group was significantly higher than that of the CPH control group (p<0.05), and the neurological deficit score was significantly lower (p<0.05). The blood rheology indices and CBF of the treatment group were better than those of the control group (p<0.05). Both treatments significantly elevated the bone mineral density (p<0.05), and the treatment group enjoyed significantly better outcomes (p<0.05). Kudiezi injection in combination with CPH could treat diabetes complicated with cerebral infarction safely and effectively.
| | NR |
| 52 | Poisoning & anesthesia | Liao | 2019 | Evaluation of the effect of using naloxone with meclofenoxate for the treatment of patients with acute severe ethanol intoxication (abstract only; in Chinese) | RCT | 150 CPH with naloxone: 75 Control naloxone: 75
| NR
| Patients with acute alcohol intoxication | CPH | NR
| NR
| NR
| After treatment, the total effective rate of patients in both groups was not significant different (p>0.05).
The time from the beginning of treatment to wakefulness and the time from the beginning of treatment to the disappearance of clinical symptoms were shorter in the combined treatment group than in the control group A (p<0.05). The treatment with naloxone and CPH for patients with acute severe ethanol was effective.
| | NR |
| 53 | Poisoning & anesthesia | Mao et al.
| 2019 | The effect of meclofenoxate hydrochloride on recovery and early postoperative cognitive dysfunction of elder female patients under general anesthesia (abstract only) | RCT
| 60 (all females) | NR
| Elderly female patients under general anesthesia (postoperative after hysterectomy) | CPH | i.v. | 250 mg
| NR
| Compared to the placebo group, eye-opening time upon calling, directional response time, oriented response time, extubation time and stay time at the post-anesthesia care unit in the CPH group were significantly shorter and Steward wakes up scoring was better (p<0.05). The scores of MMSE after 24 hours of surgery in both groups were lower than that before 24 hours of surgery (p<0.05). There was no statistical difference between the two groups (p>0.05). Compared to patients without postoperative cognitive dysfunction, POCD patients were older, lower education, higher level of ASA grading (p<0.05). CPH hydrochloride has a preventive effect on the early POCD. At the same time, it has the effect of resuscitation after general anesthesia, and the time of extubation is shorter and the sober state is better.
| NR
| NR |
| 54 | TBI & coma | Ma
| 2018 | Observation on Therapeutic Effect of Meclofenoxate Hydrochloride on Severe Traumatic Brain Injury and Its Effect on GCS Scores (abstract only) | RCT
| 102 | NR
| Patients with severe TBI | CPH | NR
| 0.6 g/day | NR
| The total effective rate in the CPH group B was higher than that in the conventional treatment group A, and the mortality rate was lower than that in group A, with statistically significant differences (p<0.05). After treatment, the GCS scores in group B were higher than those in group A, and the intracranial pressure was lower than that in group A, with statistically significant differences (p<0.05). The incidence of complications in group B was lower than that in group A, and the difference was statistically significant (p<0.05). CPH hydrochloride is effective in the treatment of severe TBI and can improve the GCS scores and promote prognosis.
| NR
| NR |
| 55 | Perinatal & pediatric | Zhang
| 2018a | Observation of the efficacy and nursing care of acupoint injection combined with gua sha in the treatment of pediatric enuresis (abstract only; in Chinese) | Randomized comparative trial | 82 | NR
| Children with enuresis
| CPH | NR
| NR
| NR
| The recent treatment efficiency of the experimental group was 92.68% (38/41) and the long-term treatment efficiency was 78.04% (32/41). While the recent treatment efficiency of the control CPH group was 80.48% (33/41) and the long-term treatment efficiency was 60.97% (25/41).
| NR
| NR |
| 56 | Stroke | Zhang
| 2018b | Clinical efficacy of meclofenoxate hydrochloride in the treatment of patients with acute cerebral hemorrhage and its effect on hs-CRP, NSE, and IL-6 levels (abstract only; in Chinese) | RCT
| 80 | NR
| Patients with ACH | CPH | NR
| NR
| NR
| After treatment, the total clinical efficacy of the observation group was 95% (38/40), which was higher than the 75% (30/40) of the control group (p<0.05). The NIHSS score was 35.7% lower than that of the control group (11.73±2.08 vs. 18.20±3.10; p<0.05), and the GCS score was 42.2% higher than that of the control group (12.84±3.01 vs. 9.0±2.1 points; p<0.05). high-sensitivity CRP, NSE, IL-6 levels were lower than those in the control group (9.02±2.18 vs. 19.34±3.02 mg/l, -53.4%; 13.40±2.10 vs. 20.35±3.01 μg/l, -34.3%; 8.49±1.23 vs. 17.96±2.97 pg/mL, -52.8%; p<0.05). The amount of cerebral hematoma in the observation group was 31.0% lower than that in the control group (18.02±1.92 vs. 26.07±2.30 mL), and the ADL score was 28.4% higher than that in the control group (75.86±9.32 vs. 59.08±8.60 points, p<0.05). It is concluded that the treatment with CPH hydrochloride in patients with ACH is effective in improving patients' neurological deficits and reducing clinical symptoms, which is beneficial to patients' prognosis.
| NR
| NR |
| 57 | Poisoning & anesthesia | Tang & Dong | 2018 | Clinical study on Xingnaojing Injection combined with meclofenoxylate in treatment of acute alcoholism (abstract only) | Comparative | 117 | NR
| Patients with acute alcohol intoxication | CPH | i.v. | 600 mg
(CPH 0.2 g dissolved in 250 mL of 5% glucose, 3x a day)
| 3 days
| After treatment, the clinical efficacy in the CPH control and treatment groups were 81.03% (47/58) and 96.61% (57/59), respectively, and there was difference between the two groups (p<0.05). After treatment, revive time, poisoning symptoms disappeared time, and exercise function recovery time in the treatment group were obviously shorter than those in the CPH control group, and there was difference between the two groups (p<0.05). After treatment, the levels of blood oxygen saturation, arterial oxygen content, superoxide dismutase, and glutathione peroxidase in the two groups were significantly increased, and the difference was statistically significant in the same group (p<0.05). The observational indexes in the treatment group were significantly higher than those in the CPH control group (p<0.05). After treatment, the incidence of discomfort symptoms in the CPH control and treatment groups were 43.10% and 13.56%, respectively, and there was difference between the two groups (p<0.05).
| NR
| NR |
| 58 | Perinatal & pediatric | Li & Kang | 2017 | Wenshenyipi combined with massage in the treatment of spleen Qi deficiency enuresis in children and its influence on sleep arousal levels of children (abstract only) | Randomized comparative trial
| 74 | NR
| Children with spleen Qi deficiency enuresis
| CPH | Oral
(capsule) | NR
| 15 days
| Compared with before treatment, the levels of plasma ADH3* decreased in the two groups after treatment, levels of plasma ADH1* increased, enuresis, lassitude, anorexia, diarrhea, sweating and other symptom scores decreased, the number and residual urine enuresis decreased, bladder capacity increased (p<0.05).
*[we are uncertain about ADH1 and ADH3]
Compared with the control CPH group, the levels of plasma ADH3 were lower, levels of ADH1 were higher, enuresis, lassitude, anorexia, diarrhea, sweating and other symptom scores were lower, the number and volume of residual urine enuresis were lower, bladder capacity were higher (p<0.05). The sleep arousal level of the study combined group was better than that of the control CPH group (p<0.05). The effective rate of the study group was better than that of the control CPH group (91.9% vs. 70.3%; p<0.05) (34/37 vs. 26/37, respectively).
| | NR |
| 59 | Perinatal & pediatric | Zhang & Zhang | 2017 | Effective evaluation on treating infantile enuresis of the Shenqi Buzu type by the Yi’nao Bushen Tuina therapy (abstract only) | Comparative trial | 45 | NR
| Children with enuresis | CPH | Oral
(capsule) | NR
| NR
| After treatment, the sleep-wake situation was better in the research group than in the control CPH group. Urinary incontinence symptoms in the two groups were improved. The total efficiency in the research group is significantly better than in the control CPH group (p<0.05).
| NR
| NR |
| 60 | Poisoning & anesthesia | Shi | 2017 | Clinical discussion of naloxone combined with meclofenoxate for resuscitation of acute severe alcohol intoxication (abstract only; in Chinese) | RCT
| 63 CPH + Naloxone: 32 Naloxone: 31
| NR
| Patients with acute alcohol intoxication
| CPH | NR
| NR
| NR
| The differences between the clinical indexes of the patients in the observation group and the control group were not statistically significant (p>0.05). The total effective rate of the observation group was 90.63% (29/32), which was statistically higher than the 74.19% (23/31) of the control group (p<0.05). The awakening time of the patients in the observation group was statistically shorter than that of the control group (p<0.05). In the rescue of patients with acute severe alcohol intoxication, the use of naloxone combined with CPH has a better rescue effect, which not only shortens the awakening time of patients, but also significantly improves the clinical symptoms of patients after awakening, so it is worth promoting the use in clinical emergency.
| NR
| NR |
| 61 | Dementia & cognitive decline | Yang & Zhang | 2016 | Clinical efficacy of gastrodin injection in the treatment of patients with cerebral atrophy (76 cases) (abstract only; in Chinese) | Comparative trial | 76 | NR
| Patients with cerebral atrophy | CPH | NR
| NR
| 3 months
| The treatment efficiency of the gastrodin group was 94.74% (36/38), and that of the control CPH group was 68.42% (26/38), the treatment efficiency of the control group was significantly lower than that of the test group (p<0.05).
| NR
| NR |
| 62 | Perinatal & pediatric | Wang | 2015 | Clinical observation on 40 cases of infantile enuresis of lung and spleen qi deficiency syndrome treated with Buzhong Yiqi Tang and Suoquan Wan (abstract only) | Randomized comparative trial | 77 | NR
| Children with enuresis (of lung and spleen qi deficiency) | CPH | Oral
(capsule) | 300 mg (3x100)
| 15 days
| After treatment, 2 groups of children with enuresis, fatigue, decreased appetite, loose stools, spontaneous perspiration and other clinical symptoms were improved in varying degrees, symptom scores decreased significantly, compared with the same group before treatment, the difference was statistically significant (p<0.05), significantly better than the control group (p<0.05). In the control CPH group, the total effective rate was 72.9% (27/37) and in the treatment group was 92.5% (37/40), the difference between the 2 groups had statistical significance (χ2=2.472, p<0.05).
| NR
| NR |
| 63 | Poisoning & anesthesia | Xu et al. | 2014 | Analysis of the efficacy of naloxone combined with meclofenoxate in the treatment of acute severe ethanol intoxication (abstract only; in Chinese) | RCT | 76 | NR
| Patients with acute severe ethanol intoxication | CPH
| NR
| NR
| NR
| Identical data as trial #83 (Sun et al., 2010). The overall efficiency was 100%. The time to consciousness in the combined group was 3.18±0.75 h, which was 22.3% shorter than that in the control group (4.09±1.28 h). The time to disappearance of symptoms was 9.68±2.88 h, which was significantly shorter (-31.7%) than that in the control group (14.18±3.65 h; p<0.01). Compared with naloxone alone, naloxone combined with CPH has a shorter time to consciousness and symptom disappearance in the treatment of acute severe ethanol intoxication, which is worthy of clinical promotion and application.
| | NR |
| 64 | Stroke
| Lin
| 2014 | Clinical efficacy of meclofenoxate in the treatment of 40 cases of acute cerebral infarction (abstract only; in Chinese) | RCT | 40
Conventional treatment + CPH: 20 Conventional treatment (oral aspirin, i.v. Danhong, dehydrating agent and control of blood glucose and blood pressure): 20
| NR
| Patients with ACI
| CPH | NR
| NR
| 3 weeks
| The total effective rate after the treatment with CPH was 85% (17/20) in the observation group and 65% (13/20) in the control group, with a significant difference between the two groups (χ2=6.21, p=0.0345). After 3 weeks of treatment, significant differences were observed (t=3.19, p=0.0418): The NIHSS was 79.2±17.6 in the observation CPH group and 69.2±19.3 in the control group (assumed a modified NIHSS was used, as this was considered an improvement).
The BI scores (Barthel index is used to assess disability) were 75.2±22.2 in the observation CPH group and 65.1±21.9 in the control group (increased by 15.5%).
The clinical effect of CPH treatment in patients with ACI is significant, which can help patients recover as soon as possible and is a safe and effective treatment method.
| NR
| NR |
| 65 | Perinatal & pediatric | Jiang et al.
| 2014 | Clinical observation of 62 cases of infantile enuresis treated with herbal fumigation and umbilical application (abstract only) | Randomized comparative trial | 118
Control CPH: 56 Treatment with herbs: 62
| NR
| Children with enuresis | CPH
| Oral
(capsule) | NR
| 28 days
| | NR
| NR |
| 66 | Perinatal & pediatric | Chen et al.
| 2013 | Clinical study of Bushen Zhiyi decoction in the treatment of children enuresis (abstract only) | Randomized comparative trial | 134
| Children
| Children with enuresis | CPH
| Oral
(capsule) | NR
| 4 weeks
| The total effective rates of the treatment group (92.71%; 89/96) were better than that of the control CPH group (78.95%; 30/38). A significant difference was shown (p<0.05) in the treatment group compared to the control group in symptoms improvements of nocturnal enuresis. A greater significant difference was shown (p<0.01) in relapse rate.
| NR
| NR |
| 67 | Urinary | Zhou et al.
| 2013 | Efficacy and effect on urodynamics of Yi Qi and Yin method in treating patients with post-stroke urinary incontinence (abstract only; in Chinese) | Comparative trial
| 60
| NR
| Patients with post-stroke urinary incontinence
| CPH
| NR
| NR
| NR
| The total effective rate was 90.0% (27/30) in the treatment group and 73.3% (22/30) in the control CPH group, and the difference between the two groups was significant (p<0.05). All urodynamic indexes in the two groups improved significantly after treatment, and the differences were significant when compared with those before treatment (p<0.05); the improvement of maximum bladder capacity, maximum forced urinary muscle pressure and bladder compliance in the treatment group was significantly better than that in the control CPH group (p<0.05).
| NR
| NR |
| 68 | Perinatal & pediatric | Guo
| 2013 | Clinical analysis of 88 cases of neonatal hypoxic-ischemic encephalopathy treated with meclofenoxate (abstract only; in Chinese) | RCT
| 88 | NR
| Patients with neonatal HIE | CPH | NR
| NR
| NR
| The total effective rate of the observation group was 95.8%. The total effective rate of the control group was 72.5%. The total effective rate of treatment in the observation group was significantly better than that in the control group (p<0.05). The NBNA score was significantly better than that before treatment in both groups (p<0.05), and the improvement of NBNA (neonatal behavioral neurological assessment) score was more significant in the observation group after treatment (p<0.05). The addition of CPH to conventional treatment is more effective in significantly reducing neuronal injury, reversing the pathogenesis of cerebral hypoxic-ischemic injury, and reducing the occurrence of sequelae.
| NR
| NR |
| 69 | Perinatal & pediatric | Shi et al.
| 2013 | Observation on clinical effect of acupoint injection combined with scraping in the treatment of infantile enuresis (abstract only) | Randomized comparative trial | 309 | NR
| Children with enuresis | CPH | Oral
| NR
| NR
| | NR
| NR |
| 70 | Poisoning & anesthesia | Mai
| 2013 | Efficacy of naloxone combined with meclofenoxate in the treatment of acute ethanol intoxication (abstract only; in Chinese) | RCT | 104
Treatment CPH + naloxone
Control naloxone
| NR
| Patients with acute alcohol intoxication | CPH
| NR
| NR
| NR
| The results showed that the time of symptom relief was reduced by 35.4% in the combined group (33.18±5.45 min) compared to the naloxone group (51.35±12.32 min).
The time of symptom disappearance was reduced by 40.6% in the combined treatment group (3.66±1.25 h) compared to the naloxone group (6.16±2.44 h).
The difference between the two groups was statistically significant (p<0.01). The efficacy of naloxone combined with CPH hydrochloride in the treatment of acute ethanol intoxication is better than that of naloxone alone and is worth promoting.
| NR
| NR |
| 71 | Metabolism & biochemistry | Xie & Min
| 2013 | Effect of nalmefene combined with meclofenoxate on recovery from general anesthesia in the elderly patients undergoing radical gynecological tumor surgery (abstract only) | RCT | 60
CPH: 20 (group A) Nalmefene: 20 (B)
Combined: 60 (C)
| NR
| Elderly patients undergoing radical gynecological tumor surgery | CPH | i.v.
| 0.25 g | 60 minutes after surgery
| Compared with group CPH A, the awakening and extubation time were decreased both in group B and group C. The awakening and extubation time were shorter in group C than in group B. But there was no significant difference in mean arterial pressure, HR and SpO2 in the 3 groups. Nalmefene combined with CPH may shorten the time of recovery from general anesthesia in elderly patients undergoing radical gynecological tumor surgery.
| | NR |
| 72 | Poisoning & anesthesia | Hu et al.
| 2013 | Observation on the efficacy and care of meclofenoxate combined with naloxone in the treatment of acute ethanol poisoning (abstract only; in Chinese) | RCT | 120
| NR
| Patients with acute alcohol intoxication | CPH
| i.v.
| NR
| Acute
| The mean awakening time was 33.8% shorter in the combined group (3.05±0.64) compared to the control group (4.61±0.99 h), which was statistically significant (p<0.05).
The symptom disappearance time was significantly shorter (34%) in the combined group than those of the control group (8.46±1.23 h vs. 12.82±0.75 h; p<0.05). The satisfaction rate of nursing quality was 95.00% and 85.00%, respectively (p<0.05). It was concluded that CPH combined with naloxone for acute ethanol intoxication could shorten the wake-up time of patients and relieve symptoms faster; targeted nursing interventions could effectively shorten the coma time of patients, reduce the incidence of safety hazards, and improve the satisfaction of emergency care quality.
| | NR |
| 73 | Dementia & cognitive decline | Dai & Li
| 2012 | Clinical observation of meclofenoxate in the treatment of chronic alcoholic corpus callosum degeneration (abstract only; in Chinese) | Open-label
| 21
| NR
| Patients with chronic alcoholism and corpus callosum degeneration | CPH
| NR
| 300-750 mg/day (0.1-0.25 g x3 a day) | NR
| 9/21 patients (42.86%) were cured, 7/21 patients (33.33%) were improved, 3/21 patients (14.29%) were ineffective, and 2/21 patients (9.52%) died. The total effective rate was (76.19%). It is concluded that the efficacy of CPH in the treatment of chronic alcoholic corpus callosum degeneration is clear and the adverse effects are low, which is worthy of clinical application.
| | NR |
| 74 | Stroke | Liang & Wang
| 2012 | Clinical observation of Ixeris sonchifolia injection combined with meclofenoxate in the treatment of diabetic patients with cerebral infarction (abstract only) | Randomized comparative trial | 120
| NR
| Diabetic patients with cerebral infarction | CPH | i.v. | CPH 0.5 g dissolved in 0.9% sodium chloride once a day | 2 weeks
| The total effective rate of the treatment group (88.3%) was statistically higher than those of the control CPH group (76.7%) (p<0.05), and the score of neurologic impairment were lower than the control group (p<0.05). The hemorheology and CBF of the treatment group were better than the control CPH group (p<0.05). Ixeris sonchifolia injection combined with CPH is reliable in the treatment of diabetes mellitus complicating with cerebral infarction.
| | NR |
| 75 | Perinatal & pediatric | Dong et al.
| 2012 | Clinical observation of 60 cases of pediatric enuresis treated by acupoint injection combined with gua sha (abstract only; in Chinese) | Comparative trial | 120
| Children
| Children with enuresis | CPH | Oral
| NR
| NR
| The short term cure rate of the treatment group was 76.67% (46/60), and the total effective rate was 91.67% (55/60). The short term cure rate of the control CPH group was 60.00% (36/60), and the total effective rate was 76.67% (46/60). The difference between the cure rate and the total effective rate of the two groups was significant (p<0.05). The long-term effect of the treatment group was 55.00% (33/60), and the total effective rate was 78.33% (47/60). The long-term cure rate of the control CPH group was 43.33% (26/60) and the total effective rate was 61.67% (37/60). The difference between the cure rate and the total effective rate of the two groups was significant (p<0.05). The near and long-term therapeutic effect of acupoint injection combined with gua sha in the treatment of pediatric enuresis is reliable and worthy of wide clinical application.
| NR
| NR |
| 76 | Poisoning & anesthesia | Yang & Li
| 2012 | The efficacy of meclofenoxate hydrochloride combined with naloxone in the treatment of acute severe alcohol intoxication (abstract only; in Chinese) | RCT | 60
| NR
| Patients with acute alcohol intoxication | CPH | i.v. | NR
| NR
| The time to consciousness and symptom elimination in the treatment group were shorter than those in the control group, and the difference between the two groups was statistically significant (p<0.05). The combined application of CPH hydrochloride injection and naloxone hydrochloride injection was effective in the treatment of severe acute alcoholism.
| NR
| NR |
| 77 | TBI & coma | Guo et al.
| 2011 | Clinical efficacy of severe traumatic brain injury treated by naloxone and meclofenoxate (abstract only) | RCT | 200
I conventional II naloxone III CPH IV naloxone + CPH
| NR
| Patients with severe head injury | CPH | NR
| NR
| NR
| Group Ⅳ (naloxone combined with CPH) showed better patient outcomes and prognosis than group Ⅰ, Ⅱ and Ⅲ (p<0.05). Group Ⅱ and Ⅲ (naloxone vs. CPH) did not show significant differences (p>0.05). Naloxone combined with CPH has better efficacy in the treatment of severe craniocerebral trauma and is worth promoting in clinical practice.
| NR
| NR |
| 78 | Poisoning & anesthesia | Huang
| 2011 | Effect of meclofenoxate for acute alcohol intoxication (abstract only) | Randomized comparative trial | 80
| NR
| Patients with acute alcohol intoxication
| CPH
| NR
| NR
| NR
| There was no statistically significant difference (p>0.05) in the time of reviving and symptom disappearing between the two groups (CPH vs. naloxone). The treatment of acute alcohol intoxication with CPH is a safe and effective therapeutic means, which can be generally used in clinical practice.
| NR
| NR |
| 79 | Perinatal & pediatric | Wang
| 2011 | Clinical efficacy of early application of meclofenoxate hydrochloride in neonatal hypoxic-ischemic encephalopathy (abstract only; in Chinese) | RCT | 60
| NR
| Neonatal patients with HIE | CPH | NR
| NR
| NR
| The total effective rate (26/30=86.67%) of the observation group was significantly higher than that of the control group (19/30=63.33%), while the incidence of sequelae (3/30=10.00%) and morbidity and mortality rate (1/30=3.33%) of the observation group were significantly lower than those of the control group (7/30=23.33% and 3/30=10.00%), and the results were statistically significant. The early application of CPH hydrochloride in the treatment of neonatal HIE has positive efficacy and few neurological sequelae, which is worthy of clinical promotion.
| NR
| NR |
| 80 | Perinatal & pediatric | Tong
| 2011 | Observations on the application of the electric bell-circuit method in enuresis in children (abstract only; in Chinese) (not included in the analysis) | Comparative trial | 198
| NR
| Children with enuresis
| CPH | NR
| NR
| 8 weeks (+6 months follow up)
| The treatment efficiency of the behavioral intervention group was higher than that of the control CPH group, and the recurrence rate and the incidence of adverse reactions were smaller than those of the control group, and the differences were statistically significant (p<0.05). The behavioral intervention of the electric bell-circuit method is effective in children with enuresis and is worth promoting.
| NR
| NR |
| 81 | Pharmacokinetics | Li et al.
| 2010 | Bioequivalence of meclofenoxate dispersible tablets and capsules in Chinese healthy volunteers (abstract only)
| Crossover randomized bioequivalence comparative trial
| 18
| NR
| Healthy male volunteers | CPH | Oral
(capsules vs tablets)
| 200 mg
| Single dose
(with 7 days washout) | The major pharmacokinetic parameters of CPH dispersible tablets and CPH capsules were as follows: Tmax: 1.8±0.3 and 2.1±0.3 h ρmax: 13.9±2.6 and 12.8±2.8 mg/L (ug/mL)
T1/2: 6.1±2.0 and 6.0±2.1 h AUC 0-t: 36±9 and 34±8 mg·h/L
AUC 0-∞: 36±9 and 35±8 mg·h/L
The relative bioavailability of the test drug was 105±10% CPH dispersible tablets and CPH capsules are bioequivalent in Chinese healthy volunteers.
| NR
| NR |
| 82 | Poisoning & anesthesia | Hou
| 2010 | Meclofenoxate in the treatment of delayed encephalopathy in carbon monoxide poisoning (abstract only) | RCT | 60
| NR
| Patients with acute CO poisoning delayed encephalopathy | CPH
| i.v. | NR
| NR
| The cure rate and the total effective rate were all improved significantly. The effectual time and the cure time were all shortened significantly in the treatment group. CPH can obviously improve acute CO poisoning delayed encephalopathy patients’ CBF dynamics and shorten the disappearance time of clinical symptoms and signs.
| NR
| NR |
| 83 | Poisoning & anesthesia | Sun et al. | 2010 | Efficacy of meclofenoxate combined with naloxone in the treatment of acute severe ethanol intoxication (abstract only; in Chinese) | RCT | 96
| NR
| Patients with acute severe ethanol intoxication
| CPH | NR | NR
| NR
| Identical data as trial #63 (Xu et al., 2014). The mean time of wakefulness in the treatment group (3.18±0.75 h) was shorter than that in the control group (4.09±1.28 h). The mean time of symptom disappearance in the treatment group (9.68±2.88 h) was shorter than that in the control group (14.18±3.65 h). The differences were statistically significant (p<0.01). It is concluded that CPH combined with naloxone has better efficacy in the treatment of acute severe ethanol poisoning and is worthy of clinical application.
| NR
| NR |
| 84 | Poisoning & anesthesia | Lv & Yuan
| 2010 | Analysis of meclofenoxate combined with hyperbaric oxygen for the treatment of acute severe carbon monoxide poisoning (abstract only; in Chinese) | RCT | 59
| NR
| Patients with acute severe CO poisoning
| CPH
| NR | NR
| NR
| The results showed that the treatment group was better than the control group in terms of improvement of clinical symptoms and improvement of cranial CT or MRI findings (p<0.05). It is concluded that CPH combined with HBO has significant efficacy in the treatment of patients with severe CO poisoning.
| NR
| NR |
| 85 | General | Chen
| 2010 | Clinical efficacy of meclofenoxate in the treatment of acute cerebral infarction in 56 cases (abstract only; in Chinese) | Randomized comparative trial | 102
| NR
| Patients with ACI
| CPH | i.v. | NR
| NR
| The results showed that blood rheology and CBF were significantly better than those in the pretreatment and control groups (p<0.05), and the clinical efficacy was statistically significantly different from that of the control group (p<0.05). It is concluded that the effect of i.v. administration of CPH in the treatment of ACI is significant and worthy of clinical promotion.
| NR
| NR |
| 86 | Stroke | Dai et al.
| 2009 | Effect of Xuesaitong injection with meclofenoxate hydrochloride on cerebral infarction (abstract only) | RCT | 92
| NR
| Patients with cerebral infarction
(within 72 hours of onset) | CPH | NR | NR
| 14 days treatment up to 3 weeks follow up
| Compared with the control group, there was a significant difference in NIHSS in the treatment group after 1 and 3 weeks (p<0.05 and p<0.01). Xuesaitong injection with CPH hydrochloride was effective and safe for cerebral infarction. Measured but results not reported:
| | NR |
| 87 | Perinatal & pediatric | Mao
| 2009 | 32 cases of pediatric enuresis treated with stopping the loss of urine soup combined with bladder function training (abstract only; in Chinese) | Randomized comparative trial | 58
| NR
| Children with enuresis | CPH | Oral
(capsule) | NR
| 4 weeks
| The cure rate was 87.5% (28/32) in the treatment group and 69% (18/26) in the control CPH group, with a significant difference between the two groups (p<0.05). The combined treatment plan has better efficacy in the treatment of pediatric enuresis, and the combination of stopping enuresis soup and bladder function training is more effective.
| NR
| NR |
| 88 | Perinatal & pediatric | Zhang et al.
| 2009 | Clinical trial of 96 cases of paediatric enuresis treated with paediatric enuresis caused by deficiency of kidney qi (abstract only; in Chinese) | Parallel DB randomized comparative trial
| 96 | NR
| Children with enuresis (kidney qi deficiency)
| CPH
| Oral
(capsule) | NR
| 28 days
| The total effective rate of pediatric enuresis granules was 94.29% (68/72 but is not accurate), and the total effective rate of the positive control CPH group was 95.65% (23/24). The results of the non-inferiority test showed that the efficacy of pediatric enuresis granules was not inferior to that of the positive control group.
The total effective rate for the TCM symptoms was 91.43%, and the total effective rate for the positive control group was 78.26%. The difference between the two groups was not statistically significant.
| | NR |
| 89 | Perinatal & pediatric | Pu & Liu
| 2008 | The clinical research of meclofenoxate in the treatment of neonatal hypoxic-ischemic encephalopathy (abstract only) | RCT | 156
| NR
| Neonatal patients with HIE | CPH | NR | NR
| NR
| The general effectiveness of the treatment group was 84.6% (66/78), compared to 16.7% (13/78) in the control group. There was a significant difference between the two groups (p<0.05). After injection of CPH, the therapeutic effect of neonates with HIE is significant and soon, sequelae of the nervous system are few, thus treatment of HIE with CPH is worth researching and generalizing.
| NR
| NR |
| 90 | TBI & coma | Gao et al.
| 2008 | The clinical observation of meclofenoxate hydrochloride in treatment of coma by craniocerebral injury (abstract only) | RCT | 200
| NR
| Coma patients caused by craniocerebral injury | CPH | NR | NR
| NR
| In the CPH group, the GCS was increased significantly compared with those in the control group (p<0.05). CPH hydrochloride is an effective choice in the treatment of coma caused by craniocerebral injury, and the adverse reactions are mild.
| |
|
| 91 | Neurological symptoms | Liu et al.
| 2008 | Meclofenoxate improves heart rate variability in patients with acute ischemic stroke (abstract only) | Randomized comparative trial | 141 (91+50)
CPH: 46
Piracetam: 45
Healthy patients: 50
| NR
| Patients with cerebral infarction
| CPH | NR | NR
| 15 days
| Compared with the healthy population, the heart rate variability indexes (SDNN, SDANN, SDNN Index, RMSSD, PNN50 and HRVTI) were significantly lower in patients with cerebral infarction (p<0.05). The indexes of HRV were significantly higher after CPH treatment than before treatment (p<0.05). SDNN, SDANN, SDNN Index were higher after piracetam treatment than before treatment (p<0.05), while RMSSD, PNN50, HRVTI did not change significantly. There was no statistical difference between the indexes of the 2 groups before treatment, and the indexes of the CPH treatment group were higher than those of the piracetam control group after treatment (p<0.05). The autonomic activity of the heart is inhibited after cerebral infarction, and CPH can improve the autonomic function of the heart after cerebral infarction, which is valuable for the prevention of cardiovascular events.
| NR
| NR |
| 92 | Poisoning & anesthesia | Wu & Zhang
| 2008 | Clinical observation of naloxone combined with meclofenoxate in the treatment of acute ethanol intoxication (abstract only; in Chinese) | RCT | | NR
| Patients with acute ethanol intoxication
| CPH
| NR | NR
| NR
| The time to symptom relief was 35.46±9.71 min and the time to symptom disappearance was 3.26±1.58 h in the combined treatment group vs. 47.25±11.62 min and 5.31±2.29 h in the naloxone group, and the comparison between the two groups was statistically significant (p<0.01). Time to symptom disappearance was 38.6% lower in the combined group.
Naloxone combined with CPH hydrochloride is satisfactory in the treatment of acute ethanol intoxication.
| NR
| NR |
| 93 | Dementia & cognitive decline | Niu & Li
| 2008 | The effect of Yizhi Xingnao Decoction on cognitive dysfunction in patients with vascular dementia (abstract only; in Chinese) | Randomized comparative trial | 80
| NR
| Patients with VaD
| CPH | NR | NR
| NR
| The total effective rate was 80% (32/40) in the treatment group and 60% (24/40) in the control CPH group, and the comparison between the two groups was statistically significant (p<0.05). In the treated group, there were statistically significant scores on the Object Memory Test (FOM) [FOME: Fuld Object-Memory Evaluation], Simple MMSE and Intellectual Disability Score (AAMD) ability scores compared with the control CPH group after treatment (p<0.05 and p<0.01).
| | NR |
| 94 | Stroke
| Wang & He
| 2007 | Effects of meclofenoxate on acute cerebral infarction (abstract only) | RCT | 156
| NR
| Patients with ACI
| CPH | i.v. | 0.3 g/day
| 14 days
| 38.5% (30/78) of patients in the test group and 29.5% (23/78) of patients in the control group had got obvious improvement. The total effective ratio of the CPH test group was significantly higher than that of the conventional treatment control group (69/78 or 88.46% vs 57/78 or 73.07%, p<0.05). CPH can be used in the treatment of ACI receiving satisfactory effection and less adverse affection.
| NR
| NR |
| 95 | Perinatal & pediatric | Ding et al.
| 2007 | The efficacy of transdermal drug delivery in 42 cases of pediatric enuresis (abstract only) | Comparative trial | 80
| NR
| Children with enuresis | CPH | Oral | NR
| NR
| In the treatment group, total effective rate 92.9% (39/42) vs Control group, total effective rate 71.1% (27/38) (p<0.05). Transdermal drug delivery integrates pharmacotherapy, electrotherapy, heat therapy and moxibustion therapy, which is effective, stable and non-toxic in the treatment of pediatric enuresis, and is well tolerated by children, and is worthy of clinical promotion.
| NR
| NR |
| 96 | Dementia & cognitive decline | Chen
| 2007b | The clinical observation of meclofenoxate in treating vascular dementia (abstract only) | DB randomized comparative trial | 60
CPH: 30 Control with VitB6: 30
| NR
| Patients with VaD
| CPH | NR | NR
| 14 days
| The general effectiveness rate of cognition capacity core of the treating group and control group was 80% (24/30) and 70% (21/30), respectively (p<0.05). The total effective rate of the nervous function defect was 80% (24/30) for CPH and 60% (18/30) for the control (p<0.01). CPH can significantly improve cognition capacity and nervous function defects in patients with VaD and with a short treating period.
| NR
| NR |
| 97 | TBI & coma | Gao et al.
| 2006 | Clinical efficacy analysis of meclofenoxate hydrochloride in the treatment of heavy craniocerebral injury (abstract only; in Chinese) | RCT | 100
| NR
| Patients with heavy craniocerebral injury | CPH | i.v. | CPH 0.5 g dissolved in 500 mL of 5% glucose solution or saline once a day
| 14 days
| There was a significant difference in the increase of GCS in the treatment group compared with the control group (p<0.05). It was concluded that the clinical efficacy of CPH hydrochloride in the treatment of heavy craniocerebral injury was accurate and safe.
| | NR |
| 98 | Psychiatry & psychology | Bian et al.
| 2006 | Meclofenoxate combined with fluoxetine vs fluoxetine alone in treatment of depression after cerebral infarction (abstract only) | RCT | 48
CPH combined with fluoxetine: 25 (12 males, 13 females) Fluoxetine alone: 23 (9 males, 14 female)
| 74±7.5 | Patients with depression after cerebral infarction | CPH | Oral (capsule) + i.v. | 300 mg/day i.v. and after 2 weeks, 600 mg/day in capsule (200 mg 3x a day)
| 6 weeks
| The total clinical effective rates in the treatment of depression were 84% (21/25) and 74% (17/23) for CPH combined with fluoxetine group and fluoxetine alone group respectively. There was no significant difference between the two groups (p>0.05). The total clinical effective rates of the recoveries of neurological function were 80% and 65% for CPH combined with fluoxetine group and for fluoxetine alone group respectively. There was also no significant difference between two the groups (p>0.05). The effects of CPH combined with fluoxetine in the treatment of depression and recovery of neurological function are the same to that of fluoxetine alone.
| NR
| NR |
| 99 | Dementia & cognitive decline | Yao et al.
| 2006 | Clinical observation of injectable meclofenoxate in the treatment of vascular dementia (abstract only; in Chinese) | Randomized comparative trial | 40
CPH: 20
Control with VitB6: 20
| NR
| Patients with VaD | CPH | i.v. | CPH 300 mg dissolved in 250 mL of 0.9% NaCl solution
| NR
| In the cognitive score: The apparent efficiency of the treatment CPH group was 35% (7/20), the effective rate was 45% (9/20), and the total effective rate was 80% (16/20). In the control group, the apparent efficiency was 20% (4/20), the effective rate was 50% (10/20), and the total effective rate was 70% (14/20). The difference between the two groups was significant (p<0.05).
In the neurological deficit score: The apparent efficiency of the treatment group was 60% (12/20), the effective rate was 20% (4/20), and the total effective rate was 80% (16/20). The apparent efficiency of the control group was 30% (6/20), the effective rate was 30% (6/20), and the total effective rate was 60% (12/20).
It was concluded that CPH i.v. was effective in improving neurological deficits and cognitive function in patients with cerebrovascular dementia, and the treatment course was short.
| NR
| NR |
| 100 | Poisoning & anesthesia | Huang & Zhang
| 2006 | Effect of meclofenoxate on the prevention and treatment of acute organophosphorus poisoning neuropathy (abstract only; in Chinese) | Single-blind RCT
| 85
CPH: 43 Control i.v. glucose: 42
| NR
| Mechanically ventilated patients with acute organophosphorus poisoning | CPH | i.v. | CPH 0.5 g dissolved in 250 mL of 5% glucose solution once per day
| 14 days
| In the treatment group, the duration of mechanical ventilation was 122.5±42.8 h. There were 4/43 cases (9.3%) of delayed peripheral neuropathy. In the control group, the duration of mechanical ventilation was 290.8±94.5 h, and there were 11/42 cases (26.2%) of delayed neuropathy. Mechanical ventilation in the treatment group was 57.9% lower than in the control group. The difference was highly significant (p<0.01). CPH has a good effect on the treatment of neurological damage in acute organophosphorus poisoning.
| NR
| NR |
| 101 | Poisoning & anesthesia | Chen et al.
| 2006 | Evaluation of the efficacy of meclofenoxate in the treatment of acute alcoholism (abstract only; in Chinese) | Randomized comparative trial | 40
| NR
| Patients with acute alcohol intoxication
| CPH | NR | NR
| NR
| The results showed that there was no significant difference between the CPH group and the naloxone group in terms of time to sobriety and time to disappearance of symptoms (p>0.05). It is concluded that CPH is not only effective and fast in treating acute alcoholism, but also has a good effect in promoting wakefulness in patients with impaired consciousness, which is worth further study and promotion
| NR
| NR |
| 102 | TBI & coma | Han
| 2005 | The efficacy of meclofenoxate hydrochloride in the treatment of post-traumatic brain injury syndrome in 26 cases (abstract only; in Chinese) | Case series
| 26
| NR
| Patients with post-TBI | CPH
| i.v. | NR
| NR
| 18 cases were cured (69.2%), 6 cases were effective, 1 case was improved, and 1 case was ineffective. CPH hydrochloride has a good effect on the treatment of post-TBI syndrome.
| NR
| NR |
| 103 | Perinatal & pediatric | Xiang & Wang
| 2005 | Clinical Study on meclophenoxate in the treatment of neonatal hypoxic-ischemic encephalopathy (abstract only) | RCT (randomization assumed) | 92 | NR
| Neonatal patients with HIE | CPH | NR | 60-100 mg/day
| 7 days
| The total curative effect in the treatment group was 43/48 cases (89. 6%), which was significantly different from that of the control group. NBNA (neonatal behavioral neurological assessment) scores and cerebral hemodynamic parameters in the treatment group were significantly different from that of the control group. CPH can obviously improve HIE children’s CBF dynamics and shorten the disappearance time of clinical symptoms and signs.
| NR
| NR |
| 104 | Immune
| Chen & Wu
| 2005 | One case of allergic reaction caused by meclofenoxate (title only; in Chinese) | Case study
| 1
| NR
| Allergic reaction
| CPH | NR | NR | NR | NR | | NR |
| 105 | Dementia & cognitive decline | Bian et al.
| 2004 | Clinical observation of meclofenoxate hydrochloride combined with huperzine A in the treatment of mild to moderate vascular dementia (abstract only; in Chinese) | RCT | 70
| NR
| Patients with VaD
| CPH | Oral
(capsule) | 0.6 g/d in 2-3 doses
| 3 months | The overall improvement rate of dementia symptoms in the combined group (23/35 or 65.71%) was better than that in the control group (13/35 or 37.14%), p<0.05. The overall improvement rate of clinical neurological deficits in the combined group (20/35 or 57.14%) was significantly better than that in the control group (8/35 or 22.85%), p<0.01. Combined application of CPH hydrochloride capsule and Huperzine A tablet can significantly improve the dementia symptoms and post-stroke neurological deficits in patients with mild to moderate VaD, and significantly improve post-stroke urinary incontinence with few adverse effects, which is a better treatment option for VaD.
| | NR |
| 106 | Stroke | Chen et al.
| 2003 | Monitoring cerebral vascular kinetic parameters to assess the efficacy of meclofenoxate in the adjuvant treatment of ischemic cerebrovascular disease (abstract only; in Chinese) | RCT | 71
| NR
| Patients with ischemic cerebrovascular disease
| CPH | Oral
| NR
| NR | According to the change in neurological deficits, the efficiency of the treatment group was 97.8%, which was significantly higher than that of the control group, which was 76.0% (p<0.05). The addition of CPH to conventional treatment can promote the recovery of brain function and improvement of brain circulation, improve the cure rate and reduce the disability rate, and improve the quality of life of patients.
| NR
| NR |
| 107 | Perinatal & pediatric | Zhu et al.
| 2003b | Efficacy of acupoint injection of 654-2 in the treatment of pediatric enuresis (abstract only; in Chinese) | Randomized comparative trial | 76
| 4-15
| Children with enuresis | CPH | Oral
| NR
| NR | The total effective rate was 85.4% (35/41) in children with enuresis treated with San Yin Jiao and Guan Yuan acupuncture points injection 654-2. The total effective rate was 51.4% (18/35) in the control CPH group. The difference between the two groups was significant (X2=9.86, p<0.05).
| NR
| NR |
| 108 | Psychiatry & psychology | Zhou
| 2002 | Clinical observation on the treatment of Alzheimer's disease with centrophenoxine (abstract only; in Chinese) | Randomized comparative trial | 80
| NR
| Patients with Alzheimer's disease (50 mild/moderate, 30 severe) | CPH
| Oral
(capsule) | 0.9 g/day
| 6 months
| The cognitive function, memory function and psychoneurological function of patients with mild and moderate senile dementia in the treatment group improved significantly compared with the control group (p<0.05), while the clinical efficacy of patients with severe dementia was poor. CPH is effective in the early treatment of Alzheimer's disease patients, with good safety, few adverse effects and is easy to take.
| NR
| NR |
| 109 | Sleep & consciousness | Ti et al.
| 2002 | Clinical application experience of centrophenoxine awakening in the treatment of sleep disorders (abstract only; in Chinese) | Open-label single-group | NR
| NR
| Patients with sleep disorder
| CPH | NR
| 0.6 g/day
(0.3 g in the morning and at noon) | NR
| 14 cases were cured, 11 cases were markedly effective, 13 cases were effective, and the total effective rate of sleep disorder treatment was 93%. CPH can improve sleep disorder.
| NR
| NR |
| 110 | Neurological symptoms | Lin
| 2001 | Observation on the efficacy of 30 cases of cerebrovascular disease treated with centrophenoxine (abstract only; in Chinese) | Open-label
| NR
| NR
| Patients with cerebrovascular disease
| CPH | Oral
(capsule) | 0.2 g 3 times/day
(before or between meals)
| 3 months
| After the treatment, the clinical symptoms, signs and laboratory test results of the patients were significantly improved compared with those before the treatment, such as the improvement rate of headache symptoms was 84.6%. CPH has obvious efficacy in improving the brain function of patients, with good safety, small side effects and easy to take, and is an effective drug for brain function recovery.
| | NR |
| 111 | Psychiatry & psychology | Xing et al.
| 1996 | A comparative study of meclofenoxate and tricyclic antidepressant in the treatment of depression (abstract only) | RCT | 51
| NR
| Patients with depression | CPH | i.v. | NR
| NR
| CPH reduced depression effectively in 92.9% of patients, of which 71.4% were markedly improved. The efficacy of combined therapy was 91.7%, of which 87.5% were markedly improved. Combined treatment had a faster onset of action. This study suggests that the combined use of i.v. CPH and oral tricyclic antidepressants are effective in depression. The use of CPH can reduce the dosage of tricyclic antidepressants and thereby reduce the latter side effects.
| NR
| NR |
| 112 | Dementia & cognitive decline | Tamai & Torii
| 1990 | Meclofenoxate provides some benefits for patients with senile dementia
(abstract only) | Case series | 20
| NR
| Patients with dementia
| Proseryl
| i.v. | 500 mg/day
| 4 weeks
| Moderate to marked symptomatic improvement was observed in 9/11 and 3/9 patients with senile dementia of the Alzheimer's type and cerebrovascular dementia, respectively. Mild improvement in a further 1 and 3 patients, respectively. No benefit from therapy in 1 and 3 patients, respectively. Symptoms of nocturnal delirium, hostility and fugue were most responsive to treatment, while somatic and neurological symptoms generally did not respond. Although the improvement rate was considered low. the authors concluded that efficacy against symptoms accompanying dementia. a good adverse effect profile and the ability to inject the drug were benefits making the CPH worthy of consideration in patients with dementia.
| | NR |
| 113 | Drug interactions
| Shimomura | 1978 | Studies of the effect of clofibrate and related compound on pituitary thyrotropin (TSH) secretion (in Japanese) | Clinical trial
| 57
Volunteers with normal thyroid function (5 males, 29 females): 34 Patients with primary hypothyroidism (4 males, 19 females): 23
| | Healthy volunteers and hypothyroidism patients
| CPH
(Dainihon Seiyaku Co)
| Oral and i.v.
| 750 mg drip infusion 600 mg/day oral
| | Patients with hypothyroidism: acute effects of CPH. In 5 patients before i.v. CPH, the serum TSH was 108.0±37.1 μU/me, the serum T3 was 85±6 ng/de and T4-I was 2.2±0.1 μg/de. The serum TSH level was below the previous value at 30 minutes after the start of MH infusion: 82% at 60 minutes, 70% at 60 minutes, 64% at 90 minutes, and 58% at 120 minutes. When CPH was not administered, there was no significant change.
Patients with normal thyroid function In six patients before 750 mg i.v. CPH, TSH was 4.6±1.2 μU/me, 4.8±0.8 μU/me at 1 hour after the start of CPH administration, and 4.8±0.8 μU/me at 2 hours. No changes were observed
Patients with hypothyroidism: after 7 days of oral CPH
Patients with normal laryngeal function:
A single and chronic administration of clofibrate (750 m/day) significantly suppressed serum TSH levels in patients with primary hypothyroidism. There was no change in serum levels of T-iodine, triiodothyronine (T) and % free T after clofibrate treatment. On the other hand, clofibrate failed to produce discernible changes in serum T-I, T, and basal and thyrotropin-releasing hormone (TRH) -induced TSH levels in euthyroid subjects. Similar results were also obtained with brain-stimulating compound CPH hydrochloride, similar in structure to clofibrate.
| NR
| NR |
| 114 | Movement disorders | Sercl & Kovarik | 1963 | On the control of Charcot's disease with centrophenoxine (ANP 235, Lucidril). Study on Amyotrophic lateral sclerosis. XIII (in German) | Parallel comparative trial
| 26
Lucidril: 13
(9 males, 4 females) Control cohort treated with trypan red: 13
(10 males, 3 females)
| 38-62 (treatment)
28-75 (control)
| Patients with ALS
| Lucidril,
ANP 235
| Oral (tablets) + i.v.
| Tablets of 0.1 g for a total daily dose of up to 0.3 g + 0.25 g i.v.
2000-3750 mg | NR
| At discharge from clinical treatment, 4 patients (30.76%) in this group were subjectively and objectively improved, 2 patients (15.38%) showed a worsening of their condition, and 7 patients (53.85%) remained unaffected by the treatment. In the 4 patients who improved, lucidril affected the clinical picture only by reducing the patient's pathological fatigue, improving the mental state and reducing muscle fasciculation. In the control trypan group, 5 patients (38.46%) improved after the end of the clinical treatment, in 3 of them were also improved and the muscle fasciculations were influenced. In a further inspection after 1 year, we found that in the treatment group 4 patients died, 3 patients did not come up and 6 patients showed a progression of the disease. In the trypan control group, 4 patients died, 3 did not come to the control and in the 6 living ones this therapy did not influence the progression of the disease. This study suggests that Lucidril had only a transient effect on certain of the symptoms, notably, on the fasciculation, on the increased pathological fatigue and the general state of the patients. Lucidril therapy cannot permanently arrest the course of the illness or materially slow it down. A comparison was made between the therapeutic results with Lucidril and the results of treatment with trypan red of a further group of 13 patients with the same disease; statistical evaluation with the X2 test showed no significant advantage for Lucidril therapy as against treatment with trypan red.
| All patients with amyotrophic lateral sclerosis tolerated the drug very well, even in the advanced stage of the disease, and in no case did the patients show individual hypersensitivity to the drug or unfavourable side-effects
| NR |
| 115 | Psychiatry & psychology | Ziolko | 1961 | Studies on the pharmacopsychological Effect of Centropkenoxin (ANP 235, Helfenberg) (in German) | Open-label
| 88
| Average age:
| Patients with neurosis
| ANP 235 (Helfenberg) | i.v. | 125 mg
| Single dose
| In the normal group, the effect of ANP 235 is indistinguishable from that of saline: the “indifferent” response predominates (45 and 50% respectively). There is also no relevant difference in the positive stimulant effect (15 and 20%) or the sedative effect (35 and 20%). It is interesting that in the neurotic group, there is a remarkable dysphoric reaction (46%, compared to compared to 5% in healthy individuals); this is always manifest by weeping, and represents a drug-conditioned release of affective-dynamic potentials, related to the back ground experience in the neurosis.
| | NR |
| 116 | Perinatal & pediatric | Neumann & Zienert | 1993 | Possibilities of treatment of intrauterine growth retardation with nootropics From Fanghanel, J., & Gossrau, R. (Eds.). (1993). Teratologie: Embryologische Grundlagen, experimentelle und klinische Teratologie. de Gruyter) (in German) | DB-RCT
| 293 (all females)
CPH (C9): 168 Placebo (C4): 125
| 17-36
| Pregnant women with growth retarded fetuses (intrauterine growth retardation from 26th to 37th week of gestation)
| Helfergin, Cerutil | Oral (tablets) | 1500 mg
(2x250 mg 3 times daily) | 6-12 weeks
| The duration of treatment, which was terminated by the birth of the child, for the placebo group was on average 6 weeks, while for the CPH group, the duration of treatment was on average 9.6 weeks. This means that the influence of CPH on the improvement of the metabolic function of the placenta or the fetus could be a reason for the prolongation of the gestation and thus the maintenance of the pregnancy. This fact is also illustrated by the completed duration of pregnancy at the time of birth: 20% of placebo subjects gave birth by the 36th week of gestation, compared to 12.9% of treatment subjects. 80% of the placebo subjects gave birth after the 37th week of pregnancy compared to 87.5% of the treated subjects. 4% of the placebo-treated subjects were delivered within the 32nd week of gestation and 0% of the treated subjects.
The birth weight distribution between the 31st to 36th week of gestation differed considerably with pregnancies with intrauterine growth retardation of the fetus. Newborns with an average weight of 1597 g were born in placebo-treated subjects. The C9 subjects newborns had an average weight of 2312 g. The average normal weight of newborns in the 32nd to 36th week of pregnancy is 2275 g, so the result after CPH treatment is identical.
The weights of the newborns between the 37th and 41st weeks of gestation differed only slightly between the placebo and the treatment group, with averages over 2800 g. 72% of the placebo-treated growth retarded neonates weighed more than 2500 g at birth, compared to 80% of the CPH-treated neonates. The pH value of the umbilical artery provides information about the condition of the newborn: Newborns from the placebo group had a higher acidosis morbidity than newborns the CPH group. 39% of placebo neonates had acidosis vs. 28% in the treatment group. 72% of CPH neonates had normal acid-base balance vs. 61% in the placebo group.
Apgar scores describe the condition of the newborn infant immediately after birth: 92% of the CPH group were in non-disordered condition after the assessment vs. 84% of the placebo group newborns. To conclude: there was an average increase in weight in the newborns treated with CPH compared to the placebo group (500-700 g) and the acid-base balance and the general condition of the newborns were healthier.
| NR
| NR |
| 117 | Poisoning & anesthesia | Mao | 2013 | The Influence of Meclofenoxate Hydrochloride on Postoperative Cognitive Dysfunction of Elder Patient under General Anesthesia (abstract only) | RCT
| 60 (all females)
| 65-80 | Elderly female patients under general anesthesia (postoperative after hysterectomy) | CPH | i.v. | NR
| 72 hours
| | NR
| NR |
| 118 | Movement disorders | Yagi et al. | 1990 | Meclofenoxate hydrochloride (lucidril) in tardive dyskinesia-a double-blind placebo-controlled study (info extracted from Tammenmaa et al., 2012) | Multicenter parallel DB-RCT
| 60
| 30-79
| Patients with tardive dyskinesia (90% with schizophrenia)
| Lucidril
| NR
| 900 mg/day | 8 weeks
| For physiological monitoring no differences between MF and placebo groups.
Tardive dyskensia assessed by AIMS. CPH was neither clearly helpful nor harmful (RR 0.89, CI 0.59-1.32).
| | NR |
| 119 | Sleep & consciousness | Wan & Bao | 1985 | A case report of Kleine-Levin syndrome (abstract only; in Chinese) | Case report
| 1
| 18
| Male farmer
| CPH
| NR
| NR
| 3 days
| After working hard in farming, the patient first appeared dizzy and heavy-headed, and the next morning he fell asleep and woke up after being called by his family, but he spoke little, his expression was indifferent, and he answered questions simply, then he went to bed again and slept, he was naturally awake when defecating and urinating, there was no incontinence, no hunger, and he was woken up by his family and ate three meals. The symptoms lasted for ten days, and then he came to our clinic and took CPH. After three days of continuous use, the symptoms were completely relieved and the intervals were as normal. Physical examination: clear consciousness, indifferent expression, lean body type, blood pressure 100/70 mmHg, normal heart and lungs, unresponsive, recent memory loss no active.
| NR
| NR |
| 120 | Pharmacokinetics
| Guddat et al. | 2006 | Detection of meclofenoxate and its degradation products Dimethylaminoethanol and p-chloro-phenoxyacetic acid | Methodological
| | NR
| Routine doping control samples (athletes)
| CPH | Oral
| 200 mg/day
| NR
| The analyses of 3000 doping control samples provide frequent detection of pCPA in approx. 5% of the analyzed samples. In none of these specimens DMAE was detected. The presence of 4-CPA was confirmed in a selection of those samples according to WADA regulations (data not shown). After oral administration of 200 mg of CPH hydrochloride, analyses of post administration urine samples provided the identification of DMAE and pCPA while CPH was not detected. CPH is rapidly hydrolyzed to DMAE and pCPA under physiological conditions. This was confirmed with the present study enabling only the detection of degradation products in post administration samples of CPH. The presence of pCPA in human urine is originating possibly from an oral intake of herbicide residues with food. The substance is utilized as an herbicide and growth regulator for plants. pCPA is considered to be absorbed completely from an oral dose and is eliminated rapidly unchanged in the urine. The second degradation product DMAE as a nootropic substance is produced naturally in the human brain and is available as a nutritional supplement. Frequent detection of pCPA in urine and the fact that DMAE occurs physiologically in the human body demonstrates the difficulty of sufficient screening for CPH. Hence an unambiguous proof of CPH misuse by identification of its degradation products requires further investigation.
| NR
| NR |
| 121 | Drug interactions | Kobayashi et al. | 1980 | Clofibrate and a related compound suppress TSH secretion in primary hypothyroidism (abstract only) | Observational | NR | NR
| Patients with hypothyroidism | CPH | i.v. | 750 mg | Single dose | A single oral dose of the hypolipidaemic agent ethyl-p-chlorophenoxyisobutyrate (clofibrate, 750 mg) produced a significant reduction in the high basal serum TSH level in patients with primary hypothyroidism. There was no consistent change in serum levels of thyroxine-iodine (T4-I), triiodothyronine (T3), and percent free T4 (%FT4) during the study. On the other hand, clofibrate failed to produce discernible changes in the basal and TRH- induced TSH secretion in euthyroid subjects. Similar results were also obtained with the centrally active drug CPH hydrochloride (750 mg, drip infusion), similar in structure to clofibrate. These findings suggest that clofibrate and CPH inhibit TSH secretion in patients with primary hypothyroidism, possibly by direct action at the hypothalamic or pituitary level.
| NR | NR
|
| 122 | Stroke | Robinson
| 1978 | Drugs acting on the peripheral circulation
| Review of controlled trials
| Trial 1: (n=260), 130 controls Trial 2: (n=30), 15 controls
| | Cerebrovascular disease
Organic dementia
| | NR
| | | Trial 1: "Lacking in a therapeutic effect". 8.4% (11/130) deaths in CPH group. 3% (4/130) deaths in the control group. No common cause of death was apparent.
Trial 2: 46.7% (7/15) deaths in CPH group. 6.7% (1/15) deaths in the control group. No common cause of death was apparent.
| | NR |
| 123 | Psychiatry & psychology | Molčan et al. | 1978 | Possible uses of nootrophic drugs in clinical psychiatry
(abstract only) | Open-label | 20
| 20-79
| Qualitative consciousness disorders | CPH | Oral | 750-2500 mg/day | NR | | NR | NR
|
| 124 | Stroke | Budinova-Smela & Mimrova | 1975 | Cetrexin in cerebrovascular diseases (abstract only) | Open-label
| 15
| NR
| | Cetrexin
| NR
| NR
| 6 weeks
| Positive results within the 1st week of treatment. The patients, all post-stroke cases, showed: Elevated 'psychic' activity [mental activity]. Elevated initiative, more cooperation in motor rehabilitation and speech reeducation.
Improvement after 6 weeks was excellent in 6/15 (40%) and marked in 9/15 (60%) patients. 15/15 (100%) participants showed improvement.
| | NR |
| 125 | Psychiatry & psychology | Qiu & Zhang
| 2003 | A comparative study on the efficacy of tricyclic antidepressants and their combined centrophenoxine in the treatment of depression (abstract only; in Chinese) | Observational
| NR
| NR
| Patients with depression
| CPH | NR
| NR
| NR
| The combination of tricyclic antidepressants with CPH was effective in the treatment of depression, and the dosage of tricyclic antidepressants was reduced with less side effects. The combination of tricyclic antidepressants and CPH is better than tricyclic antidepressant alone.
| NR
| NR |
| 126 | Urinary | Bai et al. | 2002 | Clinical efficacy of Compounded Enuresis Punch in the treatment of enuresis (abstract only; in Chinese) | Comparative | 40 Treatment group: Chinese medicine enuresis granules (ephedra, wu wei zi, cuscuta, foxglove, etc.): 20
CPH control group: 20
| NR | Patients with enuresis | CPH | NR
| NR
| NR
| TCM was superior to CPH: difference between groups p<0.05. | NR | NR
|
| 127 | Urinary | Zhu & Ren
| 1997 | Analysis of 14 cases of clozapine-induced enuresis treated by centrophenoxine (abstract only; in Chinese) | Case series
| 14 (5 males, 9 females)
| 18-52
| Patients with clozapine-induced enuresis
| CPH | NR
| NR
| NR
| | NR
| NR |
| 128 | Urinary | Yan | 1990 | A report of 5 cases of enuresis caused by clozapine treated with centrophenoxine
(abstract only; in Chinese) | Case series | 5 (all females) | 15-26 | Patients with clozapine-induced enuresis | CPH | Oral | | 2-6 | In 4 cases, the micturition stopped in 2-6 days. In 1 case, the micturition stopped after taking.
| NR | NR |
| 129 | TBI & coma | Xing & Yang
| 1991 | The efficacy of centrophenoxine in treating 13 cases of post-cranial trauma neurological syndrome (abstract only; in Chinese) | Case series
| 13
| NR
| Patients with post-cranial trauma neurological syndrome | CPH | i.v. | NR
| NR
| | NR
| NR |
| 130 | Neurological symptoms | Yang & Feng | 1987 | Exploring the treatment of cortical blindness (abstract only; in Chinese) | Case reports | 2 | 7 (only one case detailed) | Patients with cortical blindness | CPH | NR
| NR | NR | | NR | NR
|
| 131 | Perinatal & pediatric | Yang et al.
| 2007 | Analysis of the efficacy of desmopressin acetate in the treatment of primary enuresis in pediatric patients (abstract only; in Chinese) (not included in the analysis) | Comparative trial
| 445 Desmopressin: 306
CPH: 139
| NR
| Children with enuresis | CPH | NR
| NR
| | | | NR |
| 132 | Perinatal & pediatric | Jin et al.
| 2009 | Observation on the efficacy and care of desmopressin acetate in the treatment of primary enuresis in pediatric patients (abstract only; in Chinese) (not included in the analysis) | Observational | 399 | NR
| Children with enuresis | CPH | NR
| NR
| | Effective rate of desmopressin was 100%, significantly better than CPH (p<0.01) The relapse/recurrence rate is high
| | NR |
| 133 | Perinatal & pediatric | Hui & Zhang
| 2022 | Clinical study on monosialotetrahexosylganglioside sodium combined with meclofenoxate in treatment of neonatal hypoxic-ischemic encephalopathy (abstract only) | RCT
| 98
| Children
| Children with neonatal HIE | CPH | i.v. | 120 mg/day (60 twice daily)
| 7 days
| After treatment, the clinical effective rate of the combined treatment group (GM1+CPH) was significantly higher than that of the control group (97.96% vs 81.63%, p<0.05). After treatment, the improvement time of clinical symptoms in the treatment group was significantly earlier than that in the control group (p<0.05). After treatment, the serum levels of IL-6, IL-8,TNF-α, and NSE in the two groups were significantly lower than those before treatment (p<0.05), and which in the treatment group were significantly lower than those in the control group (p<0.05). After treatment, the NBNA score in the two groups was significantly higher than that before treatment (p<0.05), and which in the treatment group was significantly higher than that of the control group (p<0.05). The combination of monosialotetrahexose ganglioside and CPH hydrochloride is effective in the treatment of neonatal HIE, which can effectively reduce the inflammatory response in the brain and promote the recovery of brain nerve function.
| NR
| NR |
| 134 | Neurological symptoms | Zhao | 2004 | Observation on the curative effect of centrophenoxine in the treatment of stroke sequelae in the elderly (abstract only; in Chinese) | Observational
| 120
| NR
| Elderly stroke patients | CPH | Oral (capsules)
| Initially 0.2-3 g/day, and it could increase to 0.4-0.9 g/day after a week | 3 months
| The effective treatment rate for various symptoms of stroke sequelae in the elderly: headache 80%, dizziness 76%, tinnitus 75%, fatigue 81%, limb numbness 68%, gait instability 72%, slurred speech 48%, memory loss 82%, urinary incontinence 78%
| NR
| NR |
| 135 | Sleep & consciousness | Brezinova et al. | 1970 | The effect of centrophenoxine on EEG vigilance in the course of sleep deprivation and on the EEG pattern of all-night sleep (abstract only) | Open-label | 12 | NR | Abstinent chronic alcoholics | CPH | Oral | | During 127 hours sleep deprivation Before, during, and after a whole night sleep
| Summary of CPH effects at 1 g during sleep deprivation: CPH had a favorable effect on lower vigilance levels during the course of sleep deprivation. CPH reduced the amount of deepest slow-wave sleep stages. CPH maintained EEG arousal to stimuli for longer.
Summary of CPH effects at 750 mg after a whole night sleep: CPH prolonged the time of falling asleep. CPH reduced the amount of deepest synchronous sleep stages (stage 3+4). CPH did not reduce the amount of phase 1 REM sleep significantly.
| NR | NR |
| 136 | Movement disorders | Bradna
| 1967 | The Czechoslovak EEG Commission: The change of postural flexion pattern in cerebral palsy following centrophenoxin (lucidril) (abstract only) | Open-label | 71 patients 33 normal controls
| NR
| Cerebral palsy
| CPH | NR | NR | NR | "myotensiometric and EMG examinations...demonstrated that the plantar postural reflex, grasp reflex, and arthrokinetic reflexes of knee and hip were improved" full abstract: Discusses the influence of centrophenoxin on the CNS. Abnormal relations of flexors and extensors in postural reflex activity and spasticity may be improved as shown by myotensiometric and EMG examinations. Observations made on 71 patients and 33 normal controls demonstrated that the plantar postural reflex, grasp reflex, and arthrokinetic reflexes of knee and hip were improved. In this way the phasic and tonic behavior pattern was favorably influenced. | NR | NR |
| 137 | Perinatal & pediatric | Colpin
| 1970 | Results of treatment with centrophenoxine in a population of mentally maladjusted children (abstract available via the APA Psycinfo database with subscription) | Open-label | 35
| 6-14 years
| "normal (2), slightly or moderately retarded (4), profoundly retarded (12), imbeciles (12), or idiots (5)"
| CPH | NR | NR | 5-6 months | "40% of Group 1 (profoundly retarded to normal) and 60% of Group 2 (idiots and imbeciles) showed advancement in mental age" "Social maturity increased in 30% of both groups, and psychomotor efficiency was significantly ameliorated in 60%"
full abstract: Administered centrophenoxine (meclofenoxate) to 2 groups of 6-14 yr. old children classified as normal (2), slightly or moderately retarded (4), profoundly retarded (12), imbeciles (12), or idiots (5). Results of tests made 5-6 mo. after initiation of drug therapy indicate that 40% of Group 1 (profoundly retarded to normal) and 60% of Group 2 (idiots and imbeciles) showed advancement in mental age. Social maturity increased in 30% of both groups, and psychomotor efficiency was significantly ameliorated in 60%. The drug appeared to be well tolerated and should prove to be an important aid in training and education of the retarded | NR | NR |
| 138 | Perinatal & pediatric | Kirman
| 1961 | TRIAL OF A.N.P. 235 IN DISTURBED SEVERELY SUBNORMAL CHILDREN | DB-RCT
| 40 | Children
| Intellectual disability "patients were of low imbecile or idiot grade"
| ANP 235 | Oral | week 1: 100 mg 2x/day
week 2: 200 mg 2x/day week 3: 300 mg 2x/day week 4: 500 mg 2x/day
| 4 weeks | | NR | "thanks are due to...the Winthrop Group Ltd. for the supply of tablets" |
| 139 | Metabolism & biochemistry | Stoica et al. | 1974 | The influence of centrophenoxine and ephedrine on the hyporeactivity of the autonomic centres in patients with cerebral infarction (abstract only) | Comparative | NR | NR | Cerebral infarction | CPH | NR | NR | NR | "The reactivity of the higher autonomic centers to hypoglycemia prior to and after treatment with centrophenoxine or ephedrine in patients with cerebral infarction was studied." "Before treatment, these centers manifested reduced urinary excretion of vanillylmandelic acid (VMA) during hypoglycemia and prolonged insulin hypoglycemia was found." "Centrophenoxine administration induced in most patients a correction of the biochemical disorder (normalization of blood sugar dynamics, increased VMA urinary excretion during hypoglycemia)." "Ephedrine treatment improved the insulin blood sugar dynamics but failed to influence the VMA urinary excretion. The latter result might be due to the fact that ephedrine interferes with VMA formation so that the catecholamines released during hypoglycemia can be predominantly excreted as metanephrines." "Both CNS activating drugs were able to improve the clinical state of patients with cerebral infarction."
| NR | NR |
| 140 | Psychiatry & psychology | Vojtechovsky et al.
| 1969 | An Experimental Approach to Sleep and Aging | Open-label | | Average age: | Abstinent chronic alcoholics
| Lucidril | NR | NR | NR | Participants were subjected to sleep deprivation Fitness index (Harvard Step Test) showed a later peak in the younger group
Paired associates learning was higher at 3d relative to unmedicated controls in the CPH-treated older group only
Reactions requiring "energy-rich phosphates" (assumed to be ATP?) were increased No statistical significance was claimed for these results
| NR | NR |
| 141 | Neurological symptoms | Maeda & Ishii | 1984 | Clinical and Experimental Studies on Central Mechanisms of Visually Guided Eye and Head Movement | Open-label | 17 | NR | "Posttraumatic cervical syndrome" i.e., history of head injury 3 weeks- 1 year prior Persistent symptoms such as headache, nuchal pain, dizziness, vertigo, emotional lability, and other concomitants. | CPH | i.v. | 250 mg | Once, prior to stimulation | Outcome measures:
Abnormalities of gaze control via eye-head coordination test. Eye and head movements, gaze saccade for acquiring visual targets plus electrical stimulation of the nuchal area. Eye movement (eye angle in the head) was recorded by the electrooculogram, and the head angle in space (H) was measured using a magnet diode connected with the head. The gaze angle was also simultaneously traced on the oscilloscope.
The authors make no claim of statistical significance for any result, and no statistical significance can be calculated or inferred from the data. Graphs are presented with SD error bars only (see: https://www.graphpad.com/support/faq/spanwhat-you-can-conclude-when-two-error-bars-overlap-or-dontspan/) and only qualitative descriptions are reported in the text. No claim of clinical relevance is made; rather the authors hypothesize a mechanism for proprioception in the cervical region to affect gaze saccade latency in patients with head trauma. CPH qualitatively reduces or abolishes this effect (according to a before/after i.v. CPH comparison) but no mechanism is proposed for this result; CPH is used as a tool to help elucidate a neural pathway, rather than to establish or support a particular clinical application for CPH.
| NR | NR |
| 142 | Dementia & cognitive decline | Ma | 2014 | Effectiveness and pharmacological analysis of centrophenoxine capsules in the treatment of vascular dementia (abstract only; in Chinese) | Retrospective observational | 50 | NR | Vascular dementia | CPH | Oral | NR | NR | Compared with before treatment, the clinical indicators of patients after treatment were significantly improved, and the comparison between the two was statistically significant (p<0.05). CPH capsules has outstanding clinical therapeutic effect on patients with vascular dementia.
| | NR |
| 143 | Poisoning & anesthesia | Ji | 2009 | Clinical efficacy evaluation of centrophenoxine sobriety in the treatment of acute alcoholism (abstract only; in Chinese) | RCT | 150
| NR
| Acute alcohol intoxication | CPH
| NR | NR | NR | Compared with the routine medical treatment group, there was a statistically significant difference in the time of conscious awareness and symptom disappearance between the CPH group (p<0.01). CPH in the treatment of acute alcoholism not only has good curative effect, quick effect and good safety, but also has a good wake-up effect on patients with impaired consciousness.
| | NR |
| 144 | Perinatal & pediatric | Li | 2010 | The Clinical Research on Kidney-QI Deficiency Enuresis in Children Treated by Brain-Kidney-nourishing Tuina Manipulation (abstract only) | Randomized comparative trial | 60
| Children
| "Kidney-QI deficiency enuresis in children" | CPH | Oral | NR | Follow-up at: | | NR | NR |
| 145 | Perinatal & pediatric | Wang | 2009 | 40 Cases of Infantile Enuresis Treated by Shuleshinai Powder (abstract only; in Chinese) | Comparative | 80
| Children
| Pediatric enuresis | CPH | Oral | NR | NR | Effective rate (difference between groups p<0.05): | NR | NR |
| 146 | Perinatal & pediatric | Wei et al. | 2011 | Observation of curative effect of five-dimensional lysine combined with meclofenoxate in the treatment of 44 cases of children with enuresis (abstract only; in Chinese) (not included in the analysis) | RCT | 88
| 5-10
| Pediatric enuresis | CPH
| Oral | 450 mg/day (0.15 g/time, 3x a day) | 3 weeks | After 3 weeks of treatment, the treatment effect of group B was significantly better than that of CPH treatment group. Five-dimensional lysine combined with CPH in the treatment of infantile enuresis is more effective than CPH alone in the treatment of infantile enuresis.
| NR | NR |
| 147 | Perinatal & pediatric | Jiang | 2009 | Clinical nursing of 80 cases of children with enuresis treated with sacral hiatus group therapy combined with Xingnao Shunui Decoction (abstract only; in Chinese) (not included in the analysis) | Randomized comprative trial | 160 | Children
| Pediatric enuresis | CPH | Oral | NR
| 4 weeks | The total effective rate and recurrence rate of the first and second courses of treatment in the treatment group were better than those in the control group. It is suggested that the sacral hiatus group therapy combined with Xingnao Shunyi Decoction has a definite curative effect in the treatment of children with enuresis, which is better than that of the control CPH group, and is worthy of clinical application.
| NR | NR |
| 148 | TBI & coma | Wang et al. | 2005 | Observation on the effect of traditional Chinese medicine on cognitive impairment related to traumatic brain injury (abstract only; in Chinese) (not included in the analysis) | Randomized comparative trial | 30
| NR
| TBI-related cognitive impairment
| Teweizhi (CPH)
| Oral | 300 mg/day (100 mg 3x a day) | 6 weeks | The MMSE, Chinese Revised Adult Webster's Intelligence Scale (WAIS-RC) and ADL scores of the treatment group were significantly different from those of the control group (p<0.05). Chinese herbal medicine treatment can improve cognitive impairment related to TBI
| NR | NR |
| 149 | Dementia & cognitive decline | Yang | 2015 | Observation of curative effect of gastrodin injection on 36 cases of brain atrophy (abstract only; in Chinese) | Comparative trial | 72 Gastrodin: 36
CPH + diet: 36
| NR
| Patients with cerebral atrophy
| CPH
| i.v. | NR
| 3 months | The DRS score of the observation group after treatment was significantly higher than that before treatment and the control CPH group, and there was a significant difference. The total effective rate of patients in the observation group was 94.44% (34/36), which was significantly higher than 72.22% (26/36) in the CPH control group, and the difference between the groups was statistically significant. (p<0.05). Gastrodin injection has definite curative effect in the treatment of cerebral atrophy, and it is worthy of popularization and application.
| NR | NR |
| 150 | Poisoning & anesthesia | Xie et al. | 2020 | Effect of Xingnaojing injection combined with meclofenoxate on acute alcoholism (abstract only; in Chinese) (not included in the analysis) | RCT | 94
CPH control: 47 Xingnaojing + CPH: 47
| NR
| Patients with acute alcoholism
| CPH
| i.v. | NR
| NR | The total effective rate in the observation group was significantly higher than that in the CPH control group (p<0.05). The wake-up time and the disappearance of poisoning symptoms in the observation group were shorter than those in the control group (p<0.05). The oxyhemoglobin saturation and oxygen content of blood in the observation group after treatment were higher than those of the control group (p<0.05). The TAC and CAT were increased in the observation group after treatment, and the observation group was higher than the control group (p<0.05). The LPO in the observation group was lower than the control group after treatment (p<0.05). The incidence of discomfort after treatment in the observation group was significantly lower than that in the control group (p<0.05). Xingnaojing i.v. combined with meclofenoxate hydrochloride for acute alcoholism is effective, it can promote patients to wake up and improve symptoms, regulate poplar metabolism and oxidative stress indicators, and reduce the occurrence of discomfort after wakening.
| NR | NR |