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

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Assie MB, Sleight AJ, Koek W

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

Eur J Pharmacol. 1993 Jun 24;237(2-3):183-9.

PubMed ID

7689973 [ View in PubMed

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Abstract

The radioligand [3H]YM-09151-2 ((+/-)-cis-N-(1-benzyl-2- methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamino benzamide) 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 tubercle and the striatum (dissociation constants (KD): 36 +/- 3 pM and 26 +/- 2 pM, respectively). The total number of binding sites (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-HT2, 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Thioridazine	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details