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At least 19 recordsLinked to original sources
PubMedDate not supplied

Chlorprothixene and chlorprothixene-sulfoxide in body fluids from a case of drug overdose.

A case of fatal drug overdose involving chlorprothixene is presented. Chlorprothixene and chlorprothixene sulfoxide (CPT-SO) metabolite concentrations (mg/L) in body fluids as determined by spectrophotofluorometry were: blood, 0.10 and 0.60; bile, 3.9 and 7.0; urine, 0.4 and 3.4; and stomach contents, 340 mg and 25 mg total, respectively. Qualitative identification of chlorprothixene and CPT-SO was by thin layer and gas liquid chromatography and spectrophotofluorometry following alkaline permanganate oxidation.

Adult↗
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↗
PubMed1996

Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.

The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.

Administration, Oral↗
PubMed1981

Identification of 2-chlorothioxanthen-9-one in gastric aspirate in a case of chlorprothixene poisoning.

In gastric aspirate from a case of severe chlorprothixene poisoning, large amounts (approximately 30% of the chlorprothixene) of a previously unrecognized compound were found and identified tentatively as 2-chlorothioxanthen-9-one by combined GLC-low-resolution mass spectrometry and high-resolution mass spectrometry. The identity of the unknown compound was verified after synthesis of 2-chlorothioxan-then-9-one by two procedures. Only negligible amounts of 2-chlorothioxanthen-9-one were formed when chlorprothixene, dissolved in acids, bases, chloroform-isopropanol, methanol, or gastric fluid, was stored in the dark. However, large amounts of the drug were converted to 2-chlorothioxanthen-9-one upon exposure to UV light. Moreover, considerable quantities of unidentified degradation products were formed when chlorprothixene was exposed to lamp light as well as to UV light. Therefore, samples from cases of acute drug poisoning should be protected from light until analysis.

Chlorprothixene↗
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↗
PubMed1993

ELISA screening with GC-MS confirmation of the tranquilizer chlorprothixene administered in subtherapeutic doses to horses.

A commercially available generic promazine ELISA kit is available which shows cross-reactivity for the tranquilizer chlorprothixene (CPT). The ELISA test readily detects the presence of CPT or its metabolites in equine urine for up to 24 h after the i.v. and i.m. administration of sub-therapeutic doses (4.5 mg) to three horses. Maximum concentrations (CPT equivalents) are obtained 2 h after i.v. dosing. No distinct concentration peak values are observed after i.m. administration. Following solid-phase extraction, confirmation of CPT and its metabolites by electron impact mass spectrometry after sub-therapeutic administration is not successful. The use of chemical ionization mass spectrometry however revealed the presence of at least four metabolites including; chlorprothixene sulphoxide, hydroxylated chlorprothixene and hydroxylated chlorprothixene sulphoxide.

Animals↗
PubMed1999

Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration.

The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral administration of chlorprothixene. An integrated pharmacokinetic model and a physiological indirect pharmacodynamic/tolerance model were applied to describe the prolactin-secreting effect of chlorprothixene. A three-compartment model served as pharmacokinetic model. The pharmacodynamic and tolerance model accounted for the baseline effect, the effect induced by the drug, and the regulatory mechanism that opposes the effect of the drug. This model adequately characterized the prolactin response after intravenous and oral drug administration of each individual by the sensitivity (dissociation constant), the efficacy (maximal prolactin secretion rate), the extent, and the rate of tolerance development. We speculate that this approach improves the quality of neuroendocrine challenge tests to determine the subject's sensitivity to drugs and the time course of adaptation.

Administration, Oral↗
PubMed1981

The management of postherpetic neuralgia with chlorprothixene.

Sixteen patients with established postherpetic pain were treated with chlorprothixene. Several other pain problems were simultaneously treated. Chlorprothixene was found to produce a favorable pain response in most patients with postherpetic pain while failing to be of value in other clinical pain problems. Chlorprothixene may be a satisfactory drug for the control of spinal or ophthalmic postherpetic pain.

Acute Disease↗
PubMed2005

Determination of chlorprothixene and amitryptyline hydrochlorides by UV-derivative spectrophotometry and UV-solid-phase spectrophotometry.

Two methods for spectrophotometric determination of chlorprothixene and amitryptyline hydrochlorides were proposed. One of them is based on spectral analysis of their derivative spectra. The measurement of the value at 316.0 nm of first derivative was used for construction of calibration graph for chlorprothixene. The Beer law was obeyed in the concentration range 0.5-50.0 microg ml(-1). The amplitude of the second derivative at 261.4 nm was used for determination of amitryptyline in the range 0.5-75.0 microg ml(-1). The second proposed method is utilized the use of solid sorbent for simultaneous preconcentration and assay of studied compounds. For this purpose the filtration gel Sephadex G100 was applied. The elaborated solid-phase spectrophotometric method was used for determination of chlorprothixene at 268.0 nm in the range 2.5-75.0 microg ml(-1) and amitryptyline at 238.0 nm in the concentration range 10.0-75.0 microg ml(-1).

Amitriptyline↗
PubMed1984

Effects of chlorprothixene, haloperidol, and trifluoperazine on the delayed-matching-to-sample performance of pigeons.

The effects of chlorprothixene (4,6,8, and 10 mg/kg), haloperidol (0.13, 0.25, 0.38, and 0.5 mg/kg), and trifluoperazine (0.5, 1,2, and 3 mg/kg) were examined in pigeons responding under a delayed-matching-to-sample procedure in which delays of 0.5-, 1-, 2-, 4-, and 8-sec duration were arranged during each experimental session. Both chlorprothixene and trifluoperazine typically reduced accuracy (percent correct responses); the magnitude of this effect was generally largest at the longest delay values. Chlorprothixene was associated with an increased rate of responding to the sample stimulus in two of three subjects, whereas trifluoperazine almost always decreased response rate. Haloperidol at high doses decreased response rate, but failed to consistently impair accuracy at any dose or delay value.

Animals↗
PubMed1980

[20 years experience with chlorprothixene (author's transl)].

Chlorprothixene was the first neuroleptic of the thioxanthene group and was marketed in 1959 under the trade names of Taractan and Truxal. Since then 20 years have passed and the authors were of the opinion that it would be opportune to study the literature published during these 20 years. They perused 801 publications, hereof 542 clinical works. Of these clinical works 109 were suited for statistical analysis. They represented 7109 patients. The other publications comprise 4378 patients which means that all the literature studied consists of a total of 11487 patients. The chlorprothixene proved to be a broad-spectrum neuroleptic with good therapeutic effects. Side effects, especially the extrapyramidal symptoms, appeared only seldom. Among the 11487 patients only 1.02% showed extrapyramidal symptoms and of these only 0.05% had tardive dyskinesias. Sme evidence seems to exist that these are schizophrenic patients showing extrapyramidal symptoms, without having received neuroleptics. It is the authors' opinion that chlorprothixene is still a neuroleptic of topical interest.

Adolescent↗
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↗
PubMed2006

Sensitive spectrophotometric methods for quantitative determination of chlorprothixene in pharmaceutical dosage form.

Simple and sensitive UV-VIS spectrophotometric methods for the determination of chlorprothixene hydrochloride have been developed. One of them is based on the oxidation of chlorprothixene (CPT) by ammonium metavanadate with the formation of colourless product. The second method involves the formation of ion-pair between the drug under investigation and inorganic complexes of titanium (IV) thiocyanate followed by its extraction with mixture of butanol-chloroform (1:9, v/v). The optimum conditions for the oxidation of CPT or ion-pair formation are established. The studies are examined by UV-VIS, IR or NMR spectroscopy. The methods permit the determination of CPT over the concentration range of 2.5-25 mug/ml and 4-35 mug/ml using ammonium metavanadate or the titanium (IV) thiocyanate complex, respectively. The methods are rapid, highly reproducible and accurate with +/- 0.8%. The methods are applicable to the assay of the drug under investigation in different dosage forms and the results are in good agreement with those obtained by the official methods. Common excipients used as additives to active ingredient in pharmaceutical preparations do not interfere in the proposed methods. The extractive spectrophotometric method can be applied to the determination of chlorprothixene hydrochloride in tablets after solid phase extraction (SPE).

Antipsychotic Agents↗
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↗
PubMed1963

EFFECT OF CHLORPROTHIXENE IN PATIENTS WITH PARANOID SYMPTOMS.

Chlorprothixene, a thioxanthine derivative, claimed to have broad-spectrum antipsychotic properties, was compared with phenothiazine derivatives in the setting of a psychiatric admission service and aftercare clinic.In 32 female patients with paranoid symptoms, chlorprothixene in high dosage ranges (200 to 1200 mg. daily) was found to be as effective as similar doses of chlorpromazine in controlling the symptoms; fewer side effects were noted.

Antipsychotic Agents↗