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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
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| 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 | | 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 | | 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
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| 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
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| 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
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| 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
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| 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: | 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
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| 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.
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