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PubMed1982

[cis(Z)-Clopenthixol decanoate--a new depot neuroleptic].

cis(Z)-Clopenthixol decanoate is a new depot neuroleptic that belongs to the group of thioxanthenes. It has a duration of effect ranging from 2 to 4 weeks and it is used for long-term therapy of chronic schizophrenic patients. The aim of this review is to represent the chemistry, pharmacology, pharmacokinetics, dosage and efficacy of this drug. The target symptoms that essentially call for the application of cis(Z)-clopenthixol decanoate are hostility, suspiciousness and psychomotor restlessness. However, a distinct therapeutic effect has also been observed in patients with hallucinatory-disintegrative and manic syndromes. Moreover, the depot preparation also called forth an emotional stabilization among alcoholics as well as a mitigation of alcohol withdrawal symptoms.

Chemical Phenomena↗
PubMed1990

Controlling the retention of clopenthixol and other basic drug substances by reversed-phase ion-pair chromatography on bonded-phase materials using two counter-ions of opposite charge.

In the reversed-phase chromatography of nitrogen-containing bases on chemically bonded ODS-silica, peak tailing and prolonged retention are often considerable problems. These effects are due to residual silanols on the surface of the column material and may be remedied by adding suitable amines or quaternary ammonium ions to the eluent as anti-tailing agents. However, further addition of an anionic compound is often needed to achieve a suitable retention. The retention mechanism in such systems is complex as interaction takes place between the anionic compound and the solute molecules, anti-tailing agent and column packing material. The influence of the nature of the anti-tailing agent and anionic counter-ion on the retention of cis- and trans-clopenthixol and of other basic drug substances was investigated and it was found that both the retention and the selectivity were greatly affected.

Alkanesulfonates↗
PubMed1980

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. IV. Serum levels and clinical outcome.

Two pharmacolkinetic parameters viz. the minimum serum concentration in the dosage interval and the sera under the serum concentration curve have been correlated to 14 parameters for clinical outcome, viz. total points and factor points from the three rating scales, BPRS, CPRS, and side effects scale, in a double blind clinical trial of clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. No statistically significant correlations were observed. It is of some interest, however, that the results suggest that the treatment of individual patients with neurleptics may be adjusted by means of repeated ratings, residual percentage, changes in psychopathology, and determinations of serum concentrations. Our results do not indicate any optimal concentration range for these depot neuroleptics in the maintenance phase of schizophrenia. The so-called therapeutic window as to neuroleptics obviously varies with regard to the phase of the disease as well as the patients' social situation.

Ambulatory Care↗
PubMed1985

Local toxicity of different drugs after intramuscular or intralipomatous injection in pigs: serum concentrations after three different formulations of cis(Z)-clopenthixol.

Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro- and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)-clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma-concentration-time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general relevance.

Absorption↗
PubMed1981

Clopenthixol decanoate in schizophrenia.

Clopenthixol decanoate was given to 20 chronic schizophrenic patients for 11 months in doses ranging from 100 mg initially up to 1000 mg 3-weekly subsequently, according to clinical response and the occurrence of adverse effects. A further 3 patients received the depot injections for periods of 6 to 9 months. Improvement in individual symptoms was rated on a 4-point scale. Unwanted effects were recorded on a checklist and routine biochemical and haematological tests were carried out at the beginning and end of the treatment period. There were highly significant improvements in the mean overall symptom score and in the 5 single symptom scores (hallucinations, delusions, depression, aggressive behaviour and non-aggressive behaviour disturbance). The 2 'negative' symptoms of apathy and social withdrawal showed improvement up to 16 weeks but not at 11 months. The incidence of depression was less at the end of the study than at the time fo entry. Three patients stopped the drug after the sixth month because of extrapyramidal symptoms (2) or drowsiness (1). Three others developed severe extra-pyramidal side-effects. Unwanted effects, though recorded in 70% of patients--drowsiness and extrapyramidal symptoms were the commonest--were for the most part trivial, and were fewer and less severe than they were on entry to the study. There was no evidence of toxicity. It was considered that on the basis of this experience the drug was an effective, safe antipsychotic agent, warranting more extensive clinical trial.

Adult↗
PubMed1994

Exorcism-resistant ghost possession treated with clopenthixol.

BACKGROUND: An Indian man now in Britain explained his criminal behaviour as episodic ghost possession. Traditional exorcisms failed to help. METHOD: A 'Western' diagnosis of dissociative state or paranoid schizophrenia was made. Treatment commenced using trifluoperazine and clopenthixol. RESULTS: The patient underwent remission during neuroleptic treatment, despite previous evidence of genuine possession. CONCLUSIONS: Many cultures give rise to apparently genuine cases of ghost possession. Neuroleptics may relieve symptoms of exorcism-resistant possession.

Acculturation↗
PubMedDate not supplied

Effects of butaclamol, clopenthixol, mepromazine and cannabinol stereoisomers on apoptosis induction.

The efflux pump of multidrug resistant mdr cells have different sensitivities to some stereoisomeric forms of CNS-active compounds. The ABC transporters of mdr cells were more sensitive to (-)butaclamol than to its stereoisomeric counterpart (8), which may function to alter the membrane structure. We suppose that the drug-accessible membrane structure possesses an important role in the induction (or prevention) of apoptosis. Therefore the apoptosis-inducing effect of three stereoisomeric pairs was studied on mouse lymphoma cells. In these experiments levo- and dextromepromazine had similiar effects. The cis- and trans-clopenthixol were less effective in apoptosis induction than the 12H-benzo(a)-phenothiazine used as a positive control. The effect of stereoisomeric pairs on induced apoptosis was studied when the cells were exposed to the stereoisomers for 60 minutes before subjection apoptosis induction by benzo(a)phenothiazine, a well-known apoptosis inducer. Then the pretreated cells were exposed to 12H-benzo(a)-phenothiazine for 60 minutes. The samples were washed and incubated for 24 hours. The cells were stained with annexin-V-FITC and propidium iodine and investigated by flow cytometry. The mdr cells with increased membrane integrity may result in the preferential killing of multidrug resistant cancer cells in the presence of some stereoisomers.

Animals↗
PubMed1984

Long-term treatment of chronic schizophrenics with clopenthixol decanoate.

A study was carried out in 68 chronic schizophrenic out-patients to assess the therapeutic effectiveness and tolerance of long-term maintenance treatment with a depot preparation of clopenthixol decanoate. Patients received 200 mg to 600 mg doses by intramuscular injection every 2 to 3 weeks for a mean treatment period of 20.3 months. Clinical symptomatology was assessed at regular intervals using the Brief Psychiatric Rating Scale (BPRS) and any adverse effects were recorded against a standard check-list. The results showed that there was a significant reduction in total and factor composition BPRS scores after treatment in all patients, the improvement becoming generally evident by the sixth month of treatment. Few autonomic and neurological side-effects were reported.

Adult↗
PubMed1981

Open clinical study of cis(Z)-clopenthixol.

The antipsychotic effect and tolerance of cis(Z)-clopenthixol were studied in 13 patients with acute exacerbation of chronic schizophrenia. Seven patients were with CGI registered as improved after 28 days of treatment while 2 did not complete test treatment and the remaining 4 patients were considered unchanged. Significant average reduction of the initial total BPRS-score were registered throughout, while with NOSIE-30 a significant score reduction was seen only at day 28. The frequency of single side effects fell progressively during the treatment period. Dosages were individual and ranged at day 28 from 30 to 350 mg.

Adult↗
PubMedDate not supplied

The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.

Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed.

Adult↗