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PubMedDate not supplied

Opposite effects on human distal colon motility of two postulated alpha 2-antagonists (mianserin and chlorprothixene) and one alpha 2-agonist (clonidine).

The effects of two postulated alpha 2-antagonists (mianserin and chlorprothixene) and an accepted alpha 2-agonist (clonidine) on the distal colon motility in five healthy subjects were investigated. Opposite effects were induced by these two kinds of drugs. Distinct and characteristic motility responses were obtained from subjects with low distal colon tone and subjects with high distal colon tone. In addition, different and typical behavior responses paralleled motility changes in the two types of subjects. These results suggest that, at the doses employed in this study, both mianserin and chlorprothixene behave as alpha 2-antagonists when tested on human distal colon motility against a known alpha 2-agonist such as clonidine.

Adult↗

PubMed1987

Hemoperfusion in severe chlorprothixene overdose.

Two to twelve hours after suicidal ingestion of an estimated dose of 10 g chlorprothixene, a 31-year-old female was admitted to the emergency ward of the clinic with cardiorespiratory arrest. After successful resuscitation, the further clinical course was complicated by persistent ventricular extrasystoles and ventricular fibrillation which necessitated repeated defibrillation. Since the patient did not respond satisfactorily to supportive treatment, a combined hemoperfusion/hemodialysis was performed. Under extracorporeal detoxication, elimination of chlorprothixene from plasma was accompanied by substantial improvement of the patient's clinical condition, although only about 1.6% of the estimated dose had been removed. This case seems to indicate that evaluation of the therapeutic efficacy of hemoperfusion should not be based exclusively on the relation of the amount of the eliminated drug to total absorbed dose.

Adult↗

PubMed1976

Effects of chlorprothixene isomers on platelet 5-hydroxytryptamine receptors: evidence for different 5-hydroxytryptamine conformations at uptake and stimulatory sites.

The thioxanthene neuroleptic, cis-chlorprothixene, was approximately 200 times more potent than its transisomer as an inhibitor of the aggregation of human blood platelets induced by 5-hydroxytryptamine (5HT). Against the active uptake of 5HT by these cells, however, trans-chlorprothixene was twice as inhibitory as its cisisomer, and this inhibition was found to be competitive. It is suggested that 5HT adopts different conformations for binding to its two platelet receptors.

Binding Sites↗

PubMed1994

Quantification of chlorprothixene, levomepromazine and promethazine in human serum using high-performance liquid chromatography with coulometric electrochemical detection.

Isocratic reversed-phase high-performance liquid chromatography with coulometric electrochemical detection was optimised to quantify the neuroleptic drugs chloroprothixene, levomepromazine, and promethazine in human serum. The method involves extraction of the neuroleptic drugs in n-heptane-isoamylalcohol from the alkalinized serum, followed by chromatographic separation on a Nucleosil CN column with acetonitrile-pyridine-sodium acetate buffer as the mobile phase. The extraction recovery was > 85% for each neuroleptic drug. The sensitivity and selectivity required for pharmacokinetic studies was obtained with a dual coulometric analytical cell operating in the oxidative screen mode. The lower limit of detection in human serum for chlorprothixene, levomepromazine, and promethazine, was 0.5, 0.2 and 0.1 ng/ml, respectively. A linear relationship (r2 > 0.99) was obtained between the concentrations of each neuroleptic drug and the detector signal. The accuracy of the quality control samples was +/- 7% for each neuroleptic drug with a precision within 9.5%, 8.1% and 13.5% for chlorprothixene, levomepromazine, and promethazine, respectively. The neuroleptic drugs were stable in acetonitrile and human serum for at least six months when stored at -20 degrees C. This method is applicable to analyze a large number of serum samples for pharmacokinetic studies of the neuroleptic drugs.

Chlorprothixene↗

PubMed1996

Development of a liquid chromatographic method for the control of related substances in chlorprothixene hydrochloride.

The development of a reversed-phase liquid chromatographic method, using a mobile phase containing a mixture of anion and cation ion-pairing agents and a base-deactivated octyldecylsilyl column as stationary phase, is described for the control of all known impurities in (Z)-chlorprothixene hydrochloride (bulk drug). Validation of the method showed it to be reproducible, selective for both (Z) chlorprothixene hydrochloride and its E-isomer, accurate and linear over the concentration range of analysis with a limit of detection of 0.3 microgram ml-1.

Antipsychotic Agents↗

PubMed1989

A nuclear magnetic resonance (NMR) method for the determination of the cis/trans isomeric content of chlorprothixene.

Proton NMR spectroscopy was applied to the assignment of the isomeric identity of commercially available chlorprothixene. Nuclear Overhauser effect studies confirmed that the clinically useful isomer is the cis (Z) configuration. An NMR method for determining the isomeric content of chlorprothixene was developed based on integration of the ratio of areas of signal strength of the cis-N-methyl in comparison to the trans-N-methyl resonances.

Chlorprothixene↗

PubMed1991

Adsorptive preconcentration for voltammetric measurements of trace levels of chlorprothixene.

The psychotherapeutic drug chlorprothixene is shown to adsorb strongly onto a glassy carbon surface in an open circuit. By using this phenomenon to preconcentrate the drug at a glassy carbon electrode prior to differential-pulse voltammetric measurements, sensitivity at the ppb level is readily achieved. The adsorptive stripping response was evaluated with respect to electrolyte, solution pH, accumulation time, concentration dependence and other variables. A linear peak current-concentration relationship was observed up to 1 microgram ml-1 of chlorprothixene; the relative standard deviation (at the 0.6 microgram ml-1 level) is 3.2%. For a preconcentration time of 10 min, the detection limit was found to be 2 ng ml-1. The open circuit preconcentration/medium exchange/voltammetric scheme was used to eliminate interference from sample solutions. The application of the method to human urine samples is described.

Adsorption↗

PubMed1988

Antidepressant combination therapy of endogenous depressions with benzodiazepines or neuroleptics--a study comparing adjuvant treatment with oxazolam versus chlorprothixene.

Antidepressants are routinely administered in combination with benzodiazepine tranquilizers or low-potency neuroleptics. A controlled study was conducted involving 40 endogenous depressive inpatients who were treated with maprotiline in combination with the benzodiazepine oxazolam or the neuroleptic chlorprothixene. After a period of two weeks there was no significant difference in the clinical ratings (HRSD, Bf-S, BL, CGI) of the two groups studied. Only in the factor "anxiety" and the adjective mood scale scores was there a tendency toward quicker onset of action (third day) in the patient group treated with oxazolam, though it was not statistically significant. The clinical global evaluation (efficacy, tolerability) showed more favorable ratings for oxazolam than for chlorprothixene. Both substances were generally tolerated well; oxazolam hardly ever caused any side effects. However, a slight deterioration of some patients' conditions was observed after discontinuation of oxazolam.

Adult↗

PubMed1981

The pathophysiology of acute renal failure after chlorprothixene overdosage.

Renal failure after an overdose of chlorprothixene has been attributed to a direct nephrotoxic effect of the drug. We report a carefully investigated case. No evidence of specific nephrotoxicity was revealed and we suggest that the renal failure is due to ischaemia during a transitory syncope, a well known side-effect of chlorprothixene.

Acute Kidney Injury↗

PubMed1988

Acute oliguria associated with chlorprothixene overdosage.

The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis.

Acute Disease↗

PubMed1990

[Adsorptive stripping voltammetry of chlorprothixene at glassy carbon electrode].

A new electrochemical stripping method for measuring the antipsychotic drug chlorprothixene was reported. The drug, which was adsorbed on the surface of glassy carbon electrode, showed a sharp oxidative stripping peak at about +0.7 V (vs. Ag-AgCl) in voltammetry. The response was linear over the 0.01-1 microgram/ml concentration range. The detection limit was 2 ng/ml, about 400 times higher than UV method. The electrode surface was polished with alumina between the measurements to activate the electrode and provide good reproducibility. The open circuit accumulation/medium exchange/stripping voltammetry scheme has been proposed to avoid interference. The method has been used for direct determination of chlorprothixene in tablets and urine samples.

Chlorprothixene↗

PubMed1990

Effect of some drugs, experimental stress and estrus on unstable and fixed conditioned alimentary motor reflexes in cats. Meclophenoxate, chlorprothixen, caffeine, piracetam. Part VI.

A group of 10 cats, both sexes, were studied for the effect of peroral administration of the meclophenoxate (Cetrexin, Léciva, 1.5 mg kg-1) + chlorprothixen (Chlorprothixen, Spofa, 0.045 mg kg-1) + caffeine (Coffeinum natrium benzoicum, Spofa, 0.15 mg kg-1) combination upon the fixation of conditioned alimentary motor reflexes to a sound signal in the course of a 10-week experiment. The mentioned combination of drugs demonstrated a beneficial protective influence on the fixed alimentary motor reflexes against laboratory stress. The results were compared with the earlier fixation of the same reflexes in another group of 11 cats under piracetam (Nootropil, U.C.B. 20 mg kg-1, s.c.). In both groups of animals, the development of reflexes was performed in regular alterations of experiments under the effect of the drugs and control experiments. The drugs were administered 1 hour before the experiments. Both groups of animals showed significantly fewer intersignal and other incorrect motor reactions on the days they were given the drugs than the controls did. The number of fixed correct reactions and their latencies displayed only moderate insignificant differences between the pharmacological trials and the controls. The conclusions is that the actual development of conditioned alimentary motor reflexes was not found to be influenced by the action of the mentioned drugs modifying psychological functions and mental states.

Animals↗

PubMed1989

Chlorprothixene-induced hypouricemia: a biologic indicator of drug compliance.

Chlorprothixene is a neuroleptic as well as a potent uricosuric drug that consistently lowers the levels of plasma uric acid (PUA). The usefulness of this relative hypouricemia as an indicator of compliance with treatment was evaluated in 17 outpatients treated from 120 to 600 days. Plasma uric acid values were substantially reduced in all patients with all doses within the therapeutic range. Low levels of PUA remained stable as long as the patients were treated and returned to normal within 7 days after treatment was terminated. The authors discuss the advantages and the limitations of PUA as an indicator of chlorprothixene treatment compliance.

Adult↗

PubMed1981

[Chlorprothixene-induced central anticholinergic syndrome (author' transl)].

A case is reported in which unconsciousness and apnoea extending into the postoperative period were noted as a central anticholinergic syndrome caused by chlorprothixene. This compound was employed for preanaesthetic medication in usual clinical dosage. Physostigmine salicylate was effective in reversing the toxic side effects of chlorprothixene - an occasionally active central anticholinergic agent.

Apnea↗

PubMed1984

Presence of chlorprothixene and its metabolites in breast milk.

Chlorprothixene (CPX) and CPX sulphoxide were demonstrated in breast milk from two psychotic mothers taking 200 mg CPX daily. The milk concentrations of CPX were 120 to 260% greater than in plasma. The estimated amounts of drug administered in breast milk to one of the infants were 15 and 26 micrograms/day for CPX and CPX sulphoxide, respectively. Accordingly, the infant dose of the parent compound would be only 0.1% of the maternal dose/kg body weight. It is not likely that CPX or its metabolite would exert any immediate pharmacological effects in the nursing infant. However, the long term effect of low doses of neuroleptic drugs in the developing infants is not yet known.

Adult↗

PubMed1978

Chlorprothixene (taractan) in post-herpetic neuralgia and other severe chronic pains.

Two trials of chlorprothixene were carried out, mainly on patients with moderate to severe post-herpetic neuralgia. When the drug was given as 50 mg b.d. to outpatients, unpleasant side-effects were more important than slight effects in alleviating pain. When the drug was given as 50 mg 6 hourly to inpatients for 5 days only, there was alleviation of constant chronic pain in a third of the patients; the effect is still lasting over a period of months in a few patients. The side-effects during the course of treatment are prominent. It is concluded that the drug is worth trying in the course recommended by Farber and Burks [1] when other means of controlling postherpetic neuralgia have failed. It would be best to give the course only to inpatients.

Chlorprothixene↗

PubMed1996

Mean input times of three oral chlorprothixene formulations assessed by an enhanced least-squares deconvolution method.

The efficacy and quality of drug formulations are determined mainly by their bioavailability, which is defined by the rate and extent of drug absorption. The zero and first moments of the serum concentration time profile provide relevant information on the bioavailability. On the basis of the body residence time distributions, mean input times may be used as drug absorption rate parameters, but due to computational errors the statistical moments procedure is in some instances of limited value. To circumvent these problems we have developed a procedure to calculate mean input times from input profiles obtained by least-squares deconvolution. We enhanced the performance of the deconvolution method by directly generating initial estimates of one input rate for each sampling interval and compared the statistical properties of various input rate characteristics using data from a bioavailability study on four chlorprothixene preparations. The analysis of variance revealed that estimates of mean input times depended on the calculation procedure. Mean input times estimated by the least-squares deconvolution method were more reliable and less variable than those computed as differences of mean body residence times.

Administration, Oral↗

PubMed1987

The hypouricemic effect of chlorprothixene.

The hypouricemic effect of chlorprothixene (Taractan), a major tranquilizer from the group of thioxanthenes, was evaluated in 30 psychiatric patients who took the drug as part of their regular treatment. Levels of serum uric acid, urea, and creatinine before, during, and after the treatment were measured, as well as creatinine clearance and uric acid clearance before and during the treatment. A uricosuric effect, resembling that of probenecid, was found that exerts itself in all the patients, regardless of age, sex, diagnosis, and associated drugs. The resulting hypouricemia starts as soon as 24 hours from the beginning of treatment, stabilizes within 10 days, and averages, at that time, 48% of the initial level. It is reversible within 10 days from the end of treatment.

Administration, Oral↗