Biphasic displacement of [3H]YM-09151-2 binding in the rat brain by thioridazine, risperidone and clozapine, but not by other antipsychotics

Marie Bernadette Assié, Andrew J. Sleight, Wouter Koek

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The radioligand [3H]YM-09151-2 ((±)-cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamino benza-mide) was used to study the binding of various antipsychotic agents. Saturation experiments showed that [3H]YM-09151-2 labelled a single population of binding sites in both the olfactory tuberclee and the striatum (dissociation constants (KD): 36 ± 3 pM and 26 ± 2pM, respectively). The total number of binding (Bmax) was greater in the striatum than in the olfactory tubercle (18.1 ± 1.8 fmol/mg tissue and 5.3 ± 0.9 fmol/mg tissue respectively). Risperidone and thioridazine displaced [3H]YM-09151-2 in a biphasic manner in both brain regions, and clozapine also produced biphasic displacement curves in the olfactory tubercle but not in the striatum. All other dopamine D2 receptor antagonists tested displaced [3H]YM-09151-2 in a monophasic manner in both brain regions, in agreement with previously published data. Biphasic displacement did not appear to result from interactions with either the dopamine D3, dopamine D4, 5-HT1C or the 5-HT1A receptor binding sites. It is suggested that thioridazine, risperidone and clozapine might discriminate between different affinity states and/or subtypes of the dopamine D2 receptor which may be different from the recently identified D2short and D2long receptors.

Original languageEnglish (US)
Pages (from-to)183-189
Number of pages7
JournalEuropean Journal of Pharmacology
Volume237
Issue number2-3
DOIs
Publication statusPublished - Jun 24 1993

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Keywords

  • Antipsychotics
  • Biphasic displacement
  • Dopamine D binding
  • DopamineD receptors
  • Neuroleptics
  • [H]YM-09151-2

ASJC Scopus subject areas

  • Pharmacology

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