Page last updated: 2024-11-05

clopenthixol

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Description

Clopenthixol is a typical antipsychotic medication used to treat schizophrenia and other psychotic disorders. It is a thioxanthene derivative and acts as a dopamine receptor antagonist, blocking the action of dopamine in the brain. Clopenthixol is effective in reducing positive symptoms of psychosis, such as hallucinations and delusions. It is available in oral, injectable, and depot formulations. Clopenthixol is synthesized through a multi-step process involving reactions with thioxanthene derivatives. Its effects on the brain include reducing dopamine activity and modulating other neurotransmitter systems. Clopenthixol is studied for its potential efficacy in treating schizophrenia and other psychotic disorders, as well as its mechanism of action and potential adverse effects.'

Clopenthixol: A thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

clopenthixol : A thioxanthene derivative having a chloro substituent at the 2-position and an alkylidene group at the 10-position with undefined double bond stereochemistry. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID12454
CHEMBL ID3989892
SCHEMBL ID121819
MeSH IDM0004622

Synonyms (19)

Synonym
NCI60_013633
sordinol
ay 62021
982-24-1
nsc64087
2-[4-[3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol
clopenthixol
n-746
c22h25cln2os
SPBIO_002986
PRESTWICK1_000998
PRESTWICK0_000998
SCHEMBL121819
DTXSID9048223
(z)-clopenthixol
2-(4-(3-(2-chloro-9h-thioxanthen-9-ylidene)propyl)piperazin-1-yl)ethanol
AKOS030242398
CHEMBL3989892
Q413000

Research Excerpts

Overview

Zuclopenthixol is a thioxanthene derivative which acts as a mixed dopamine D1/D2 receptor antagonist. It is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days.

ExcerptReferenceRelevance
"Zuclopenthixol is an antipsychotic available as oral and long-acting injectable (LAI) formulations. "( Impact of age and CYP2D6 genotype on exposure of zuclopenthixol in patients using long-acting injectable versus oral formulation-an observational study including 2044 patients.
Høiseth, G; Molden, E; Smith, RL; Tveito, M, 2021
)
1.59
"Zuclopenthixol is a thioxanthene-based neuroleptic. "( [Zuclopenthixol benzoate poisoning in a child: evidence from chromatography].
Boimond, N; Cheron, G; Menager, C, 2013
)
1.73
"Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). "( Zuclopenthixol versus placebo for schizophrenia.
Jayaram, MB; Lacey, M, 2015
)
1.86
"Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. "( Economic evaluation of zuclopenthixol acetate compared with injectable haloperidol in schizophrenic patients with acute psychosis.
Gariepy, L; Kennedy, W; Lachaine, J; Laurier, C; Tessier, G,
)
1.16
"Zuclopenthixol is a thioxanthene derivative which acts as a mixed dopamine D1/D2 receptor antagonist. "( An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice.
Manzaneque, JM; Navarro, JF,
)
1.1
"Zuclopenthixol acetate is a novel and potentially useful treatment alternative in the acutely disturbed patient. "( Long-acting antipsychotic medication, restraint and treatment in the management of acute psychosis.
Fitzgerald, P, 1999
)
1.02
"Zuclopenthixol proved to be a potent antimanic, anti-aggressive and antidelusional neuroleptic already from the second day of injection."( Open multicentre trial of zuclopenthixol in mania and schizophrenia based on the AMDP scales.
Bobon, D; Bourdouxhe, S; Gilson, H; Kempeneers, JL; Mirel, J; Pedersen, V; Toussaint, C; Troisfontaines, B; von Frenckell, R; Xhenseval, B,
)
0.98

Effects

ExcerptReferenceRelevance
"Zuclopenthixol also has the advantage for both patients and nursing staff that dosage is once daily."( Zuclopenthixol, melperone and haloperidol/levomepromazine in the elderly. Meta-analysis of two double-blind trials at 15 nursing homes in Norway.
Elgen, K; Fuglum, E; Nygaard, HA, 1992
)
1.56

Toxicity

ExcerptReferenceRelevance
" The results of this study suggest that the in vitro tests employed can be useful as screening tests for local toxic effect of intramuscular drug preparations."( Tests for local toxicity of intramuscular drug preparations: comparison of in vivo and in vitro methods.
Bagdon, RE; Højelse, F; Svendsen, O, 1985
)
0.27
"Priapism has been described as a rare side effect of certain phenothiazine antipsychotics with high alpha1-adrenergic blocking potential."( Recurrent priapism as a side effect of zuclopenthixol decanoate.
Kropman, RF; Meinhardt, W; Moehadjir, D; van Hemert, AM, 1995
)
0.56
" Adverse events related to movement disorders were reported in 3%."( Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics.
Eerdekens, E; Eerdekens, M; Jacko, M; Turner, M, 2004
)
0.32

Pharmacokinetics

ExcerptReferenceRelevance
" The pharmacokinetic profiles of the three injectable zuclopenthixol preparations are very different."( Pharmacokinetics of three different injectable zuclopenthixol preparations.
Aaes-Jørgensen, T, 1989
)
0.78
" The enanthate produces peak plasma concentrations on days 2 to 3 and declines with an apparent elimination half-life (i."( Clinical pharmacokinetics of the depot antipsychotics.
Ereshefsky, L; Jann, MW; Saklad, SR,
)
0.13
" Moreover pharmacokinetic data increasingly have been clinically applied."( Chemotherapy with neuroleptics. Clinical and pharmacokinetic aspects with a particular view to depot preparations.
Knudsen, P, 1985
)
0.27
"Precise pharmacokinetic data of long-acting neuroleptics: apparent half life (T 1/2), time of peak plasma concentration (Tmax), bioavailability, has been a major contribution to determine optimal dosage of the drug."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.13

Bioavailability

ExcerptReferenceRelevance
" The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate."( Clinical pharmacokinetics of the depot antipsychotics.
Ereshefsky, L; Jann, MW; Saklad, SR,
)
0.13
" Optimal dose has been determined from the bioavailability of the oral formulation and the interval between two injections, it averages 15, 20 times the oral daily dose for haloperidol decanoate."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.13
" Hence it seems likely that concomitant food intake enhances the bioavailability of zuclopenthixol, without influencing its absorption rate."( Influence of food intake on the bioavailability of zuclopenthixol.
Aaes-Jørgensen, T; Liedholm, H; Melander, A, 1987
)
0.75

Dosage Studied

Clopenthixol (Sordinol, Ciatyl) in small dosage has been shown to be much more effective than all other types of therapy in the management of those psychoses. ZuclopenthIXol has the advantage for both patients and nursing staff that dosage is once daily.

ExcerptRelevanceReference
" Zuclopenthixol also has the advantage for both patients and nursing staff that dosage is once daily."( Zuclopenthixol, melperone and haloperidol/levomepromazine in the elderly. Meta-analysis of two double-blind trials at 15 nursing homes in Norway.
Elgen, K; Fuglum, E; Nygaard, HA, 1992
)
1.63
" Dosage was chosen and adjusted to the individual patient's condition and response."( Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.
Eliander, H; Heikkilä, L; Pedersen, V; Turunen, M; Vartiainen, H, 1992
)
1
" The dosage ranged from 50 mg to 100 mg."( Zuclopenthixol acetate in viscoleo in acutely disturbed psychotic patients.
Barr, F; Schlosberg, A, 1991
)
1
" Patients were treated until the acute episode was considered terminated by the clinician and, although dosage could be adjusted to allow optimum clinical response, the majority received 25 mg zuclopenthixol dihydrochloride 3-times daily throughout the trial period."( A clinical assessment of zuclopenthixol dihydrochloride (Clopixol tablets) in the treatment of psychotic illness.
Clayton, AR; Mann, BS; Moslehuddin, KS; Owen, RT; Rohatgi, KK; Sud, P; Vaddadi, KS, 1985
)
0.76
"Precise pharmacokinetic data of long-acting neuroleptics: apparent half life (T 1/2), time of peak plasma concentration (Tmax), bioavailability, has been a major contribution to determine optimal dosage of the drug."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.13
"Seventeen outpatients were treated with depot neuroleptics, zuclopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil, with dosage intervals of 3 weeks."( Comparative study of the pharmacokinetics of zuclopenthixol decanoate and fluphenazine decanoate.
Ba, B; Durand, A; Gouezo, F; Hou, N; Jørgensen, A; Viala, A, 1988
)
0.77
"One hundred and sixteen mentally handicapped patients with behavioural disorders were studied in a double-blind clinical comparison of zuclopenthixol decanoate injection (mean dosage 123 mg/week) and placebo."( Zuclopenthixol decanoate in the management of behavioural disorders in mentally handicapped patients.
Izmeth, MG; Khan, SY; Kumarajeewa, DI; Shivanathan, S; Veall, RM; Wiley, YV, 1988
)
1.2
" The dosage of trans(E)-clopenthixol was optimized through a pharmacokinetic study, and the suppression of the growth of Plasmodium berghei in vivo was tested in mice, with chloroquine acting as the positive and saline as the negative control."( Effect of trans(E)-clopenthixol on Plasmodium berghei in vivo.
Andersen, BJ; Jepsen, S; Kristiansen, JE; Kurtzhals, JA, 1988
)
0.91
" During the 10-week study, the dosage of zuclopenthixol dihydrochloride tablets could be adjusted to obtain optimum clinical benefit."( Acute functional psychoses: treatment with zuclopenthixol dihydrochloride ('Clopixol') tablets.
Bhattacharyya, SN; Ghoshal, J; Halstead, N; John, B; Launer, MA; Mukherjee, PK; Sharma, SK; Zigmond, AS, 1987
)
0.8
" Maximum concentrations appeared at 1 week after administration of cis(Z)-clopenthixol decanoate, whereas the highest concentrations after fluphenazine decanoate were seen at the end of the 3-week dosage interval."( Blood and plasma kinetics of cis(Z)-clopenthixol and fluphenazine in psychiatric patients after intramuscular injection of their decanoic esters.
Ba, B; Berda, C; D'Agostino, N; Dufour, H; Durand, A; Hou, N; Jørgensen, A; Viala, A, 1984
)
0.77
") was given intramuscularly to nine schizophrenic patients with dosage intervals of 1 or 2 weeks."( Serum concentrations of the isomers of clopenthixol and a metabolite in patients given cis(Z)-clopenthixol decanoate in viscoleo.
Aaes-Jørgensen, T; Danneskiold-Samsøe, P; Jørgensen, A; Kirk, L; Petersen, E, 1983
)
0.54
"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."( Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels.
Jrgensen, A; Overø, KF, 1980
)
2.01
" 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."( Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. IV. Serum levels and clinical outcome.
Dencker, SJ; Jørgensen, A; Malm, U; Overø, KF, 1980
)
1.7
" ratio about 2; maximum after 3-7 days) clopenthixol levels were recorded through-out the dosage interval."( A specific method for assay of drug levels in serum of patients treated with clopenthixol decanoate injections.
Overø, KF, 1980
)
0.76
" 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."( Serum concentrations of cis(Z)- and trans(E)-clopenthixol after administration of cis(Z)-clopenthixol and clopenthixol to human volunteers.
Aaes-Jørgensen, T, 1981
)
0.8
" The aim of this review is to represent the chemistry, pharmacology, pharmacokinetics, dosage and efficacy of this drug."( [cis(Z)-Clopenthixol decanoate--a new depot neuroleptic].
Sieberns, S; Spechtmeyer, H, 1982
)
0.7
" Clopenthixol (Sordinol, Ciatyl) in small dosage has been shown to be much more effective than all other types of therapy in the management of those psychoses."( [Treatment of pharmacotoxic psychoses with clopenthixol in patients with Parkinson's disease (author's transl)].
Danielczyk, W, 1981
)
1.44
" S-Zu was measured in 17 patients and dosage reduction was suggested by the laboratory if S-Zu exceeded 15 nmol/L."( Search for a therapeutic range for serum zuclopenthixol concentrations in schizophrenic patients.
Kjølbye, M; Olesen, OV; Rehfelt, E; Rogne, T; Thomsen, K, 1994
)
0.55
"0 and was independent of the dosage given."( Fluctuation of serum zuclopenthixol concentrations in patients treated with zuclopenthixol decanoate in viscoleo.
Larsen, NE; Olesen, OV; Poulsen, JH, 1994
)
0.6
" There were no significant metabolic or organic cerebral changes that could have accounted for the symptoms which presumably had been induced by the drugs even though their dosage was not unusual."( [Drug-induced asterixis].
Leblhuber, F; Rittmannsberger, H, 1994
)
0.29
" The dosage was changed in most of these patients (80-90%) in order to bring the concentration within the therapeutic level."( [The effect of serum monitoring on concentration of perphenazine and zuclopenthixole].
Olesen, OV; Poulsen, JH; Thomsen, K, 1993
)
0.52
" If this finding can be confirmed in a larger population, genotyping may become an important tool for the dosing of these two neuroleptic agents."( The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol.
Aberg-Wistedt, A; Bertilsson, L; Dahl, ML; Jerling, M; Landell, NE; Liljenberg, B; Sjöqvist, F, 1996
)
0.51
" The mean dosage of zuclopenthixol acetate by injection, foreseen in the protocol, was between 126 to 138 mg."( [Efficacy of zuclopenthixol acetate on psychotic anxiety evaluated in an open study].
Benyaya, J; Dermain, P; Greslé, P; Grignon, S; Moisan, P; Nore, D; Pech, G; Perret, I; Romain, JL,
)
0.8
" The aim of the study was to find out whether age at onset of schizophrenia is related to the dosage of typical neuroleptics in outpatients."( Age at onset of schizophrenia and neuroleptic dosage.
Dernovsek, MZ; Tavcar, R, 1999
)
0.3
" Neuroleptic dosage was converted to milligrams of chlorpromazine equivalents and logarithmically transformed to obtain normal distribution."( Age at onset of schizophrenia and neuroleptic dosage.
Dernovsek, MZ; Tavcar, R, 1999
)
0.3
" The average dosage was 251."( Age at onset of schizophrenia and neuroleptic dosage.
Dernovsek, MZ; Tavcar, R, 1999
)
0.3
" The method was successfully applied to the determination of these compounds in dosage forms and biological fluids."( Flow-injection chemiluminometric determination of some thioxanthene derivatives in pharmaceutical formulations and biological fluids using the [Ru(dipy)3(2+)]-Ce(IV) system.
al-Tamimi, SA; Alwarthan, AA; Aly, FA, 2001
)
0.31
" Age, sex, psychiatric and somatic diagnoses, body mass index (BMI), dosage and duration of Zuclopenthixol-acetate medication and the timing of the changeover from intramuscular to oral prescription, the single dosage of Clopenthixol if initially coadministered, incidence, onset and duration of transient benign hyperthermia, iron, ferritin, transferrin and saturation values, and white and red blood cell counts as well as liver function and electrolytes were registered."( Zuclopenthixol-acetate treatment in catatonic patients: the implication of iron metabolism.
Bertsch, E; Conca, A; Hansen, M; Hrubos, W; König, P; Küng, A; Waschgler, R, 2003
)
1.26
" This dosage should be varied depending on health, age, and temperament of the individual cheetah."( Evaluation of long-term sedation in cheetah (Acinonyx jubatus) with perphenazine enanthate and zuclopenthixol acetate.
Huber, C; Slotta-Bachmayr, L; Walzer, C, 2001
)
0.53
" During the study period, there was no change in the administration and number of psychotropics, but there was an increase in the dosage of antipsychotics."( Antipsychotic medication and length of stay at a psychiatric maximum-security unit in Norway (1987-2000).
Rasmussen, K; Renkel, S, 2006
)
0.33
" Correlations with clinical efficiency measures appeared to be contradictory for dosage and serum concentrations, respectively."( Therapeutic drug monitoring of zuclopenthixol in a double-blind placebo-controlled discontinuation study in adults with intellectual disabilities and aggressive behaviour.
Glaser, T; Haessler, F; Hiemke, C; Reis, O; Schwarz, V; Thome, J, 2014
)
0.68
" In one case, a reduction in the dosage of clonazepam was also suggested."( Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder.
Bertschy, G; Carminati, F; Carminati, GG; Chabert, J; Darbellay, B; Deriaz, N; Fathi, M; Ferrero, F; Gerber, F; Kosel, MM, 2016
)
0.43
" These patients require close monitoring for adverse effects with adjustment of dosing to ensure the optimal balance of risk versus benefit while the patient is acutely psychotic."( Polysubstance-induced relapse of schizoaffective disorder refractory to high-dose antipsychotic medications: a case report.
Harvey, R; Kekulawala, S; Kent, M; Mostafa, S; Tucker, MG, 2016
)
0.43
" No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge."( Olanzapine intramuscular shows better efficacy than zuclopenthixol acetate intramuscular in reducing the need for restraint, but not in comparison to haloperidol intramuscular.
Bloemhof-Bris, E; Shelef, A; Sinai, O; Stryjer, R; Weizman, S, 2022
)
0.97
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
H1-receptor antagonistH1-receptor antagonists are the drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine.
serotonergic antagonistDrugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonergic agonists.
alpha-adrenergic antagonistAn agent that binds to but does not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous alpha-adrenergic agonists. alpha-Adrenergic antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
dopaminergic antagonistA drug that binds to but does not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists.
first generation antipsychoticAntipsychotic drugs which can have different modes of action but which tend to be more likely than second generation antipsychotics to cause extrapyramidal motor control disabilities such as body rigidity or Parkinson's disease-type movements; such body movements can become permanent even after treatment has ceased.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
N-alkylpiperazine
primary alcoholA primary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has either three hydrogen atoms attached to it or only one other carbon atom and two hydrogen atoms attached to it.
thioxanthenesThioxanthene and its substitution derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Research

Studies (377)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990178 (47.21)18.7374
1990's68 (18.04)18.2507
2000's72 (19.10)29.6817
2010's49 (13.00)24.3611
2020's10 (2.65)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 29.20

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index29.20 (24.57)
Research Supply Index6.20 (2.92)
Research Growth Index4.36 (4.65)
Search Engine Demand Index42.09 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (29.20)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials84 (20.49%)5.53%
Reviews25 (6.10%)6.00%
Case Studies81 (19.76%)4.05%
Observational2 (0.49%)0.25%
Other218 (53.17%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (5)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics for the Prevention of Relapse in Long-term Stabilized Schizophrenic Patients: a Randomized, Single-blind, Longitudinal Trial [NCT02307396]Phase 421 participants (Actual)Interventional2015-02-01Completed
Atypical Antipsychotics and Hyperglycemic Emergencies: Multicentre, Retrospective Cohort Study of Administrative Data [NCT02582736]725,489 participants (Actual)Observational2012-04-30Completed
Effects of Classical and Atypical Antipsychotics on Dopamine Receptor Binding of 123I-epidepride, Cognition, Startle Response and Extrapyramidal Side-effects in Drug-naive First-episode Schizophrenic Patients [NCT00206960]56 participants (Actual)Interventional1998-01-31Completed
Randomized Multicentric Open-label Phase III Clinical Trial to Evaluate the Efficacy of Continual Treatment Versus Discontinuation Based in the Presence of Prodromes in a First Episode of Non-affective Psychosis. [NCT01765829]Phase 3104 participants (Anticipated)Interventional2012-11-30Recruiting
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
[information is prepared from clinicaltrials.gov, extracted Sep-2024]