General pharmacology of clozapine - PubMed

Affiliations

• PMID: 1358127

Review

General pharmacology of clozapine

D M Coward. Br J Psychiatry Suppl. 1992 May.

Abstract

Clozapine shows neuroleptic-like inhibition of locomotor activity and conditioned avoidance responding in rodents, although tolerance develops on repeated treatment. EEG-based studies show strong arousal-inhibiting activity of clozapine as well as neuroleptic-like effects on both caudate spindle duration and rat sleep-waking patterns. Effects such as apomorphine blockade, catalepsy and strong increases of plasma prolactin levels are not seen, however, and chronic treatment does not lead to dopamine D2 receptor supersensitivity. Binding studies show clozapine's highest affinities to be for dopamine D4, 5-HT1C, 5-HT2, alpha 1, muscarinic and histamine H1 receptors, but moderate affinity is also seen for many other receptor subtypes. Microdialysis studies indicate a preferential interaction with striatal D1 receptors, whereas autoradiographical studies indicate upregulation of D1 and downregulation of 5-HT2 receptors after chronic clozapine. Clarification of the mechanisms underlying clozapine's special attributes is often hampered by a failure to examine compounds which show a close chemical relationship to clozapine, but which produce extrapyramidal side-effects in man, such as clothiapine, loxapine and amoxapine.

Similar articles

• A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes.

  Singh AN, Barlas C, Singh S, Franks P, Mishra RK. Singh AN, et al. J Psychiatry Neurosci. 1996 Jan;21(1):29-35. J Psychiatry Neurosci. 1996. PMID: 8580115 Free PMC article.

• S18327 (1-[2-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperid-1-yl]ethyl]3-phenyl imidazolin-2-one), a novel, potential antipsychotic displaying marked antagonist properties at alpha(1)- and alpha(2)-adrenergic receptors: II. Functional profile and a multiparametric comparison with haloperidol, clozapine, and 11 other antipsychotic agents.

  Millan MJ, Brocco M, Rivet JM, Audinot V, Newman-Tancredi A, Maiofiss L, Queriaux S, Despaux N, Peglion JL, Dekeyne A. Millan MJ, et al. J Pharmacol Exp Ther. 2000 Jan;292(1):54-66. J Pharmacol Exp Ther. 2000. PMID: 10604931

• The role of alpha2-adrenoceptor antagonism in the anti-cataleptic properties of the atypical neuroleptic agent, clozapine, in the rat.

  Kalkman HO, Neumann V, Hoyer D, Tricklebank MD. Kalkman HO, et al. Br J Pharmacol. 1998 Aug;124(7):1550-6. doi: 10.1038/sj.bjp.0701975. Br J Pharmacol. 1998. PMID: 9723970 Free PMC article.

• [Dopamine D4-receptor variants, schizophrenia and clozapine therapy].

  Ewald HL, Mors NP, Rosenberg R. Ewald HL, et al. Ugeskr Laeger. 1996 Jun 17;158(25):3601-3. Ugeskr Laeger. 1996. PMID: 8693618 Review. Danish.

• Dopaminergic and serotonergic effects of clozapine. Implications for a unique clinical profile.

  Meltzer HY, Gudelsky GA. Meltzer HY, et al. Arzneimittelforschung. 1992 Feb;42(2A):268-72. Arzneimittelforschung. 1992. PMID: 1586397 Review.

Cited by

• Clozapine-induced locomotor suppression is mediated by 5-HT2A receptors in the forebrain.

  McOmish CE, Lira A, Hanks JB, Gingrich JA. McOmish CE, et al. Neuropsychopharmacology. 2012 Dec;37(13):2747-55. doi: 10.1038/npp.2012.139. Epub 2012 Aug 8. Neuropsychopharmacology. 2012. PMID: 22871913 Free PMC article.

• Neuropharmacological profile of an atypical antipsychotic, NRA0562.

  Hirota S, Kawashima N, Chaki S, Okuyama S. Hirota S, et al. CNS Drug Rev. 2003 Winter;9(4):375-88. doi: 10.1111/j.1527-3458.2003.tb00261.x. CNS Drug Rev. 2003. PMID: 14647530 Free PMC article. Review.

• The Use of Ascorbic Acid in Adjunctive Treatment for Schizophrenia-Current State of Knowledge.

  Piłat P, Nikel K, Smolarczyk J, Piegza M. Piłat P, et al. Life (Basel). 2024 Jun 28;14(7):828. doi: 10.3390/life14070828. Life (Basel). 2024. PMID: 39063582 Free PMC article. Review.

• Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine.

  Beeler JA, Burghardt NS. Beeler JA, et al. J Exp Neurol. 2021 Mar;2(1):21-28. J Exp Neurol. 2021. PMID: 33768216 Free PMC article.

• Necrotising colitis related to clozapine? A rare but life threatening side effect.

  Leong QM, Wong KS, Koh DC. Leong QM, et al. World J Emerg Surg. 2007 Aug 21;2:21. doi: 10.1186/1749-7922-2-21. World J Emerg Surg. 2007. PMID: 17711574 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Other Literature Sources

  • The Lens - Patent Citations Database