title: Biphasic displacement of [3H]YM-09151-2 binding in the rat brain by thioridazine, risperidone and clozapine, but not by other antipsychotics.
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.
authors.affiliation: Neurobiology Division II, Centre de Recherche Pierre Fabre, Castres, France.
authors.forename: M B
authors.initials: MB
authors.lastname: Assié
authors.forename: A J
authors.initials: AJ
authors.lastname: Sleight
authors.forename: W
authors.initials: W
authors.lastname: Koek
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003024:Clozapine / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000378:metabolism*; D008297:Male; D009833:Olfactory Pathways / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone; D013134:Spiperone / Q000378:metabolism; D013881:Thioridazine / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D065127:Dopamine D2 Receptor Antagonists; D007555:Isoxazoles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D013134:Spiperone; D003024:Clozapine; D018967:Risperidone; D013881:Thioridazine; C030265:nemonapride