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At least 19 recordsLinked to original sources

PubMed1987

Penfluridol, chlorprothixene and haloperidol block fast axonal transport in an order of potency consistent with a mechanism related to inhibition of calmodulin.

The effects of the inhibitors of calmodulin penfluridol, chlorprothixene and haloperidol on fast axonal transport, the content of adenosine triphosphate and creatine phosphate and the density of axonal microtubules, were measured in spinal nerves of the bullfrog in vitro. These drugs inhibited the fast orthograde transport of [3H]leucine-labelled proteins: 35 microM penfluridol, 70 microM cis-chlorprothixene, and 200 microM haloperidol were needed to produce and approximately 50% inhibition of transport, and the order of potency was, therefore, penfluridol greater than cis-chlorprothixene greater than haloperidol; the trans isomer of chlorprothixene was as effective as the cis isomer-of chlorprothixene in inhibiting fast axonal transport. None of these drugs significantly reduced the density of microtubules in unmyelinated axons of nerves, incubated as for a transport experiment. Exposure to the concentration of these drugs which inhibited transport did not reduce significantly the content of adenosine triphosphate of the nerves, except for a 22% reduction by trans-chlorprothixene, and they had no significant effect on the content of creatine phosphate except for a 27% reduction by penfluridol and a 20% reduction by trans-chlorprothixene. The inhibition of axonal transport by these drugs can therefore not be explained either by an interference with oxidative metabolism or by disruption of microtubules. The order of potency of penfluridol, chlorprothixene and haloperidol as inhibitors of fast axonal transport parallels their known order of potency as antagonists of calmodulin; inhibition of axonal transport may therefore be related to inhibition of the function of calmodulin by these drugs.

Adenosine Triphosphate↗

PubMed1990

Bromazepam in generalized anxiety. Randomized, multi-practice comparisons with both chlorprothixene and placebo.

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits -0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as "at least good" in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.

Adolescent↗

PubMed1989

Anticholinergic effects of cis-chlorprothixene characterized in rat parotid acini.

The anticholinergic effects of the antipsychotic drug, cis-chlorprothixene, on the secretory events underlying the formation of primary saliva were investigated. The neuroleptic, cis-chlorprothixene, is used extensively as a major tranquillizer but shares side-effects such as xerostomia with most antidepressants. The inhibitory effects of cis-chlorprothixene upon the cholinergic-induced rise in Ca2+ as well as on O2 consumption and Cl- loss were investigated in isolated rat parotid acini in order to characterize its anticholinergic effects quantitatively. The cholinergic-induced rise in cytosolic, free Ca2+ was inhibited by cis-chlorprothixene with half-maximal effect at 1.9 microM and maximal inhibition at 10 microM. When the cytosolic, free Ca2+ was enhanced in the presence of 10 microM cis-chlorprothixene by means of the Ca2+ ionophore A23187, a loss of Cl- was observed similar to that observed during cholinergic stimulation in the absence of cis-chlorprothixene. The findings are consistent with the possibility that cis-chlorprothixene exerts its effects on the steps leading from agonist binding to the acetylcholine receptor and to the increase of cytosolic free Ca2+. Thus, measurement of the stimulation-induced rise in cytosolic, free Ca2+ in the presence of neuroleptics such as the thioxanthenes represents a fast and reliable method for detecting inhibitory effects on autonomic receptor activation.

Animals↗

PubMed1985

Determination of chlorprothixene and its sulfoxide metabolite in plasma by high-performance liquid chromatography with ultraviolet and amperometric detection.

This communication describes a rapid, sensitive and selective method for the assay of chlorprothixene and its sulfoxide metabolite in human plasma, using reversed-phase high-performance liquid chromatography. Alkalinized plasma was extracted with heptane--isoamyl alcohol (99:1), after addition of thioridazine as the internal standard. The residue obtained after evaporation of this extract was chromatographed on a cyano column, using acetonitrile--0.02 M potassium dihydrogen phosphate pH 4.5 (60:40) as the mobile phase with ultraviolet (229 nm) detection. Quantitation was based on peak height ratios over the concentration range of 5.0-50.0 ng/ml for both compounds with 85% and 90% recovery for chlorprothixene and its sulfoxide metabolite, respectively, using a 1.0-ml plasma sample. The assay chromatographically resolves chlorprothixene and the sulfoxide metabolite from the N-desmethyl metabolite, which can only be semi-quantitated owing to low and variable recoveries. The method was used to obtain plasma concentration versus time profiles in two subjects after oral administration of 100 mg of chlorprothixene suspension and in two additional subjects following overdosages of chlorprothixene estimated to exceed several hundred milligrams. These analyses demonstrated that the sulfoxide metabolite is the predominant plasma component following therapeutic administration and overdosages. High-performance liquid chromatography with oxidative amperometric detection with the glassy carbon electrode was also evaluated. Although this procedure demonstrated comparable sensitivity and precision to ultraviolet detection for the analysis of chlorprothixene and N-desmethyl chlorprothixene, the sulfoxide metabolite could not be measured with high sensitivity (less than 100 ng/ml) owing to endogenous interferences. Hence the utility of this alternative assay technique is limited.

Adult↗

PubMed1991

Three-dimensional structure and molecular dynamics of cis(Z)- and trans(E)-chlorprothixene.

cis(Z)-Chlorprothixene has antidopaminergic potency, while trans(E)-chlorprothixene is virtually inactive. In order to reveal the structural features causing the difference in activity, the three-dimensional molecular and electronic structures of cis(Z)- and trans(E)-chlorprothixene were examined by computer graphics and molecular mechanical and quantum mechanical calculations. The internal molecular motions of the isomers were studied by molecular dynamics simulations in vacuo and in aqueous solution. The cis(Z)-isomer had lower potential molecular energy than the trans(E)-isomer, mainly due to electrostatic interactions within the side-chain and between the dimethylamino group and the chlorine atom. During molecular dynamics simulations in aqueous solution, the side-chain of the trans(E)-isomer stayed closer to the central S-C axis of the ring system than did the side-chain of the cis(Z)-isomer. The molecular electrostatic potentials were significantly lower in the vicinity of the chlorine atom in the trans(E)- than in the cis(Z)-isomer. Differences in molecular electrostatic potentials and in three-dimensional structure are suggested to be the main reasons for the difference in pharmacological activities of cis(Z)- and trans(E)-chlorprothixene.

Chlorprothixene↗

PubMed1992

Polyneuropathy caused by chlorprothixene.

Seven chronic psychiatric patients developed signs of polyneuropathy mainly in the lower limbs after receiving chlorprothixene (500-1800 mg/d) from 3 to more than 24 months. The most prominent electroneuromyographic findings were decreased or not measurable motor conduction velocities of the peroneal nerves. Electromyography showed signs of denervation in the leg muscles in all the patients, and also in the upper limbs in 4 of them. The signs of polyneuropathy gradually subsided after withdrawal of chlorprothixene. Thus, chlorprothixene may cause a toxic, dose-dependent, reversible polyneuropathy.

Adult↗

PubMed1986

Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video-controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Nordic Dyskinesia Study Group.

Thirty-three chronic psychiatric patients with tardive dyskinesia (TD) were included in a video-controlled multicenter study of the effect of chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden in TD and parkinsonism. The drugs were given in a cross-over design in randomized order in dosages equipotent to the earlier neuroleptic treatment and administered for periods of 6 months with 6-week placebo periods before and after. A total of 55 treatment periods were completed; only seven patients were able to go through all three treatment phases (= 96 weeks). Perphenazine (20.5 mg/day), haloperidol (5.5 mg/day), and haloperidol (11 mg/day) + biperiden (7 mg/day) induced a moderate suppression of TD and at the same time produced a corresponding aggravation in parkinsonism. Chlorprothixene (142 mg/day) had only a slight TD reducing effect and did not change parkinsonism. Thus the TD suppressing effect was inversely related to the parkinsonian-inducing effect of the neuroleptics. Following withdrawal of the drugs, TD increased in some cases and decreased in others compared to the pretreatment level. No significant correlation was found between the intensity of the withdrawal TD and either drugs or preceding parkinsonism or TD suppression. Only in a subgroup of seven patients who consecutively received all three neuroleptics, perphenazine, but not haloperidol and chlorprothixene, produced a post-treatment aggravation which was correlated to the parkinsonsim and TD suppression during treatment. Independent of the neuroleptic given, the TD intensity increased significantly from the first to the third placebo period. This suggests that drug holidays are inappropriate to prevent TD induction/aggravation.

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↗

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↗

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↗

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↗

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↗