title: [Pharmacology of antipsychotics at human dopamine D2 and D3 receptors].
abstract: Aripiprazole is a dopamine D/D3 and serotonin 5-HT1A receptor partial agonist which is approved for treatment of schizophrenia. We evaluated the pharmacological properties of aripiprazole, dopamine D2 receptor partial agonists and antipsychotics using forskolin-stimulated cAMP accumulation in cells expressing human dopamine D2 and D3 receptors. In cells expressing high densities of D2 receptor with high sensitivity for dopamine, the maximal agonist effects of partial agonists were higher than in cells expressing low densities of D2 receptor with low sensitivity for dopamine. Aripiprazole's intrinsic activities at D2 and D9 receptors were lower than those observed with partial agonists (terguride, bifeprunox, OPC-4392 and (-)-3-PPP), which demonstrated clinically suboptimal improvement of positive symptoms of schizophrenia patients, and higher than that of SDZ 208-912, which demonstrated incidence of extrapyramidal symptoms similar to haloperidol. Aripiprazole's appropriate intrinsic activities at D2 and D: receptors may contribute to desired results in a clinical profile. Antipsychotics (risperidone, olanzapine, amisulpride, sulpiride and perphenazine) which displayed antidepressive effects in schizophrenia patients behaved as preferential antagonists in cells expressing D2 receptors compared to cells expressing D3 receptors. Preferential antagonism at dopamine D2 receptors may play a role in the antidepressive effects of these antipsychotics.
authors.affiliation: Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, Japan. y_tadori@research.otsuka.co.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tadori
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kikuchi
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000068180:Aripiprazole; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D005576:Colforsin; D000068180:Aripiprazole