title: [The affinities of mosapramine for the dopamine receptor subtypes in human cell lines expressing D2, D3 and D4 receptors].
abstract: The affinities of mosapramine hydrochloride, an iminodibenzyl antipsychotic drug, for dopamine receptor subtypes were determined by human dopamine D2, D3 and D4 receptors expressed in several cell lines and compared with those of other neuroleptics. Tritiated spiperone bound to the membrane of transfected cells in a saturable manner, and the Kd values for dopamine D2, D3 and D4 receptors were 0.021, 0.12 and 0.10 nM, respectively. Mosapramine showed the highest affinities for these receptor subtypes among the antipsychotics tested. The ratio of Ki values between D2 and D3 (D2 Ki/D3 Ki ratio) in mosapramine was higher than that of haloperidol, indicating that the effects of mosapramine on D3 receptors were more potent than those of haloperidol. On the other hand, clozapine, risperidone and raclopride had higher affinity to D4, D2 and D3 subtypes, respectively. The affinities of mosapramine for D4 receptors was 8 times higher than that of clozapine, and the affinity for D3 receptors was 40 times higher than that of raclopride. These results suggest that the effect on D3 receptors may underlie at least a portion of mosapramine's atypical clinical profile.
authors.affiliation: Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Futamura
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Haga
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism*; D001552:Benzazepines / Q000378:metabolism*; D002460:Cell Line; D003024:Clozapine / Q000378:metabolism; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D018967:Risperidone / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; C493599:DRD4 protein, human; C493605:DRD5 protein, human; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C046384:mosapramine; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D020891:Raclopride; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone