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At least 19 recordsLinked to original sources
PubMed1981

Serum levels of the isomers of clopenthixol in patients given cis(Z)-clopenthixol or cis(Z)/trans(E)-clopenthixol.

The serum levels of the two geometric isomers of clopenthixol and N-dealkylated clopenthixol were estimated in 9 patients, who received cis(Z)-clopenthixol (Cisordinol, Clopixol tabl.) in one period and the double dose of cis(Z)/trans(E)-clopenthixol (Sordinol, Ciatyl) in another period. Nearly equal concentrations of the neuroleptically active isomer, cis(Z)-clopenthixol, were found in the two periods. This finding is in agreement with the clinical experience, but in disagreement with the administered amounts of cis(Z)-clopenthixol, which were larger when the cis(Z)-isomer was given alone. Highly significant correlations were found between dose and mean serum level of cis(Z)-clopenthixol and between dose and area under the serum concentration curves for 8 of the patients, the ninth patient, who had received additional medication showed deviating results. No indication of transformation of cis(Z)-clopenthixol into trans(E)-clopenthixol or vice versa was found. Trans(E)-clopenthixol was found in the serum samples even after administration for one week with the cis(Z)-clopenthixol tablets indicating a relatively long half-life of the trans(E)-isomer. The cis(Z)-isomer of N-dealkyl clopenthixol was found in about the same concentration as cis(Z)-clopenthixol in both periods, while trans(E)-N-dealkyl clopenthixol occurred in about 4 times higher concentrations in patients who had either been given cis(Z)/trans(E)-clopenthixol before they went into the study or had received it in the first period of this study.

Adult↗
PubMed1981

Serum concentrations of cis(Z)- and trans(E)-clopenthixol after administration of cis(Z)-clopenthixol and clopenthixol to human volunteers.

The serum concentrations of cis(Z)- and trans(E)-clopenthixol have been estimated in human volunteers by an HPLC-method after administration of a clopenthixol tablet, which contains the cis(Z)- and the trans(E)-isomers in the ratio 1/2, or a cis(Z)-clopenthixol tablet. The serum concentration curves obtained for the cis(Z)-isomer after administration of the two drug preparations were very similar, and thus independent of the presence of the trans(E)-isomer in one of the preparations. Likewise the biological half-lives and the areas under the serum concentration curves for cis(Z)-clopenthixol were similar after the two preparations. The biological half-life of cis(Z)-clopenthixol was as a mean 20 hours (12-29 hours) indicating that from a pharmacokinetic point of view a dosage interval of 24 hours is possible for most patients. The biological half-life of trans(E)-clopenthixol is found to be longer than that for cis(Z)-clopenthixol.

Adult↗
PubMed1977

Pharmacokinetic studies on clopenthixol decanoate; a comparison with clopenthixol in dogs and rats.

The release from the depot, hydrolysis and distribution in the organsim as well as the metabolism and elimination of intramuscularly injected clopenthixol decanoate in Viscoleo have been studied in dogs and rats with radioactive as well as non-labelled drug after single as well as repeated administration. The studies clearly demonstrate the depot effect of clopenthixol decanoate given intramuscularly in oil compared to orally administered clopenthixol. The amounts of drug remaining at the site of injection in dogs suggest monoexponential release of drug from the depot and a half-life of 4-5 days. Rapid hydrolysis to clopenthixol in the organism was indicated by in vitro experiments and in vivo findings. Clopenthixol was found to be the main compound in the organism after single as well as repeated doses. The clopenthixol formed by hydrolysis appeared to be metabolized in the same way as clopenthixol given orally i.e. by dealkylation of the side chain and by S-oxide and N-oxide formation. The elimination pattern with predominant fecal excretion also appeared to be the same after clopenthixol and its esterified derivative apart from the reflection in the latter case of the slow release from depot. A rapid exchange in the organism between tritium from the drugs and hydrogen from the body water was demonstrated. This has to be considered in studies with tritium labelled drugs, where estimation of total radioactivity gives the sum of tritium in drug, metabolites and water.

Administration, Oral↗
PubMed1981

A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients.

The therapeutic effect of the neuroleptic cis(Z)-clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double-blind 8-week trial. Forty-nine of the 54 patients in the trial received clopenthixol in the pre-trial period. Ratings with CGI and a single side effects form were done at weeks 0, 2, 4, 6, and 8. The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)-clopenthixol with patient's functioning than by clopenthixol. The ratio of therapeutically equipotent cis(Z)-clopenthixol/clopenthixol doses was found to be 1:2. It is suggested that long-term treatment with clopenthixol advantageously may be replaced by cis(Z)-clopenthixol.

Adult↗
PubMed1978

Cis(Z)-clopenthixol and clopenthixol (Sordinol) in chronic psychotic patients. A double-blind clinical investigation.

The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 2-month double-blind trial were included 57 psychotic patients, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning, as well as any individual side effects were done at months 0, 1, and 2. The antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Apart from the finding that the unspecific sedative effect appeared to be less marked with cis(Z)-clopenthixol, the type, degree, and frequency of side effects were the same in the two groups of patients. More than half of the patients experienced no side effects.

Adult↗
PubMed1981

Cis(Z)-clopenthixol and clopenthixol in the treatment of acute psychoses and exacerbations of chronic psychoses. A double-blind clinical investigation.

The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 4-week double-blind trial were included 20 patients with acute psychoses and exacerbations of chronic psychoses, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning were done at weeks 0, 2, and 4, at which occasions also the BPRS was filled in. All patients improved, most of them so much that their final BPRS-score was less than half their initial score. In conclusion, the antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Side effects were few, similar, and equally frequent in the two groups, extrapyramidal side effects and drowsiness being the most common.

Adult↗
PubMedDate not supplied

Concentrations of cis(Z)-clopenthixol and trans(E)-clopenthixol in a lethal case involving zuclopenthixol, diazepam, and cyamemazine.

cis(Z)-Clopenthixol and trans(E)-clopenthixol were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography-diode-array detection in necropic samples from a postmortem case. The peripheral blood concentrations of cis(Z)-clopenthixol and trans(E)-clopenthixol were 278 and 177 ng/mL, respectively. The level of the active cis(Z)-isomer is within the toxic range. Other associated drugs' concentrations were within their therapeutic ranges. Postmortem redistribution of the drug and instability of the drug due to trans-isomerization were discussed.

Adult↗
PubMed1983

Serum concentrations of the isomers of clopenthixol and a metabolite in patients given cis(Z)-clopenthixol decanoate in viscoleo.

Cis(Z)-clopenthixol decanoate in Viscoleo (Sordinol Depot, Cisordinol Depot, Clopixol Inj.) was given intramuscularly to nine schizophrenic patients with dosage intervals of 1 or 2 weeks. Serum concentrations of the two geometric isomers of clopenthixol and its N-dealkyl metabolite were recorded in two successive dosage intervals. Significant correlations were found for dose vs area under the serum concentration curve and vs serum concentrations measured on individual days. The last mentioned concentrations are good measures of the area under the serum concentration curve, which expresses the drug load of the patient. The serum concentration curves in two successive dosage intervals were very similar. Maximum serum concentration was seen 5-7 days after injection and the mean maximum/minimum fluctuation was 1.6 with the 2-week dosage interval. The finding of very low amounts of the trans(E)-isomers of clopenthixol and the N-dealkyl-metabolite shows that isomerization of the cis(Z)-compounds into the corresponding trans(E)-isomers does not take place within the organism.

Adult↗
PubMed1980

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.

Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug.

Adult↗
PubMed1983

Dopamine and mania. The effects of trans- and cis-clopenthixol in a double-blind pilot study.

Sordinol is composed of the mixture of cis-clopenthixol and trans-clopenthixol. The two isomers do not differ in several pharmacological properties, for instance anti-noradrenergic effect. However, cis-clopenthixol possesses anti-dopaminergic effects, while trans-clopenthixol does not. Sordinol-depot contains the almost pure cis-clopenthixol and appears to be less sedating than the oral and short-lasting intramuscular administration forms. In a double-blind pilot study with 10 manic patients, trans-clopenthixol was compared with cis-clopenthixol. Although not reaching statistical significance, cis-clopenthixol showed anti-manic effects, while trans-clopenthixol remained ineffective. It is concluded that the anti-dopaminergic effect of cis-clopenthixol is essential for its anti-manic effect, which is in agreement with the hypothesis of involvement of the dopaminergic system in the pathogenesis of mania.

Affective Disorders, Psychotic↗
PubMed1987

The antibacterial activity of the psychopharmacological agent clopenthixol and its two main metabolites.

The antibacterial effect of the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol and the two main metabolites of clopenthixol in man, N-dealkyl-clopenthixol and clopenthixol sulfoxide, was examined in 24 Gram-positive and 37 Gram-negative bacterial strains in vitro. The antibacterial potency of the drugs towards the Gram-positive strains, measured as IC50, was: N-dealkyl-clopenthixol, 6.2 microM (3.7 micrograms/ml), trans(E)-clopenthixol, 16 microM (7.6 micrograms/ml) and cis(Z)-clopenthixol, 37 microM (17.5 micrograms/ml), and clopenthixol sulfoxide was inactive in the investigated area. Against the Gram-negative strains the drugs are less potent. A therapeutic application of these results, especially in the case of trans(E)-clopenthixol, which possesses no neuroleptic activity, requires in vivo testing in an animal model. However, the in vitro model employed might also be useful in the study of such agents and other membrane-active compounds with regard to their interaction with biological membranes.

Anti-Bacterial Agents↗
PubMed1980

A specific method for assay of drug levels in serum of patients treated with clopenthixol decanoate injections.

A fluorimetric method is presented for the simultaneous and specific assay in serum of clopenthixol decanoate, clopenthixol and a clopenthixol metabolite, deprived of the ethanol group in the side chain. The separation is achieved by extractions and thin layer chromatography and fluorescence brought about by treatment with sulphuric acid. The limit of detection in 3 ml serum samples is about 2 ng/ml for clopenthixol and mtabolite, and somewhat higher for the ester. In addition serum data are presented for patients treated with intramuscular injections of 100-600 mg clopenthixol decanoate in Viscoleo every second week. Relatively stable (mean max./min. ratio about 2; maximum after 3-7 days) clopenthixol levels were recorded through-out the dosage interval. Somewhat lower metabolite levels were found. There was no evidence for the presence of clopenthixol decanoate.

Clopenthixol↗
PubMed1977

Pharmacology of cis(Z)-clopenthixol decanoate, a depot neuroleptic.

The duration and intensity of the neuroleptic effect of cis(Z)-clopenthixol decanoate in Viscoleo have been compared with those of cis(Z)-clopenthixol, 2 HCl in aqueous solution in a number of animal experimental models. Cis(Z)-clopenthixol, 2 HCl had a strong, but short-lasting neuroleptic effect (apomorphine antagonistic effect in dogs, inhibition of conditioned avoidance response in rats) which was accompanied by marked sedation. In contrast, cis(Z)-clopenthixol decanoate in oil had an effect which was slower in onset, but of much longer duration and only the highest doses caused a slight sedation. In rats catalepsy could be induced in some animals by high doses of cis(Z)-clopenthixol decanoate whereas cis(Z)-clopenthixol, 2 HCl at all the doses tested caused catalepsy in all animals. In mice only high doses of cis(Z)-clopenthixol decanoate in oil caused reduction of spontaneous motor activity and potentiation of barbiturate anaesthesia. The results are discussed with special reference to the clinical use of the depot preparation.

Administration, Oral↗
PubMed1980

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels.

Serum concentrations of clopenthixol and flupenthixol have been determined during a four weeks dosage interval in patients treated with intramuscular injections of clopenthixol decanoate or flupenthixol palmitate in Viscoleo. Maximal drug levels were attained by the end of the first week after injection of either preparation. A period of exponential decline was then recorded. The half-lives were estimated to 19 days for clopenthixol and 17 days for flupenthixol. These half-lives most likely refer to the rate of release from the oil depot and not to elimination of drug. The mean ratio between maximal and minimal drug levels was 2.5 for clopenthixol and 3.7 for flupenthixol. Systemic clearance was estimated to about 0.7 l/min and 0.5 l/min, respectively. Significant correlation was found between the administered doses and recorded serum levels, between doses and estimated areas under the serum concentration curves, and also between areas and drug levels. The data indicate more limited individual variability than that seen with other psychotropic drugs, given orally. The study clearly demonstrates, that significant serum levels of active drug is maintained throughout the dosage interval by intramuscular injection of clopenthixol decanoate or flupenthixol palmitate in Viscoleo every fourth week.

Ambulatory Care↗
PubMed1985

The susceptibility of Plasmodium falciparum in vitro to chlorpromazine and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol.

New antimalaria drugs are needed on the background of increasing resistance to chloroquine. This study was undertaken to elucidate whether other membrane stabilizers than chloroquine have anti-malarial activity in vitro. We here report the anti-plasmodial activity of chlorpromazine (CPZ) and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol. As a screening method we used a modified Desjardins' 3H-hypoxanthine assay. The IC50 = 50% inhibition of 3H-hypoxanthine uptake was found at 1.028 ng/ml = 3.2 microM CPZ, 758 ng/ml = 1.6 microM trans(E)-clopenthixol and 436 ng/ml = 0.9 microM cis(Z)-clopenthixol. The inhibitory effect of trans(E)-clopenthixol in these low concentrations on Plasmodium falciparum in vitro seems particularly promising, since it is known that trans(E)-clopenthixol has no neuroleptic effect.

Animals↗
PubMed1985

In vitro modulation of human neutrophil chemotaxis by cis(Z)- and trans(E)-clopenthixol, and chlorpromazine.

Phenothiazines have been shown to depress several functions of neutrophils, including chemotaxis. A biphasic effect of chlorpromazine (CPZ) and other phenothiazines on human neutrophil chemotaxis has recently been described. We investigated the effect of the stereo-isomers of clopenthizol, a thioxanthene, and of CPZ on human neutrophil chemotaxis. CPZ, at a concentration of 157 microM, and cis(Z)- or trans(E)-clopenthixol, at 105 microM, decreased cell viability. Cis(Z)- and trans(E)-clopenthixol as well as CPZ exerted a biphasic effect on neutrophil chemotaxis with a maximal enhancement of 57%, 92%, and 119%, respectively, and inhibition at higher concentrations. Enhancement of human neutrophil chemotaxis and possibly of the antibacterial activity of these cells by CPZ and the stereo-isomeric compounds of clopenthixol may have clinical implications especially in immunocompromised hosts. The enhancing effect of trans(E)-clopenthixol is of particular importance as this stereo-isomer of clopenthixol exhibits both antimicrobial and antiplasmodial activity but has no antipsychotic or antihypersecretory effect.

Bacterial Infections↗