The investigation for relation between the mechanism of P-glycoprotein and treatment-resistant schizophrenia effective Clozapin

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461742
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: kenichi osada 聖マリアンナ医科大学, 医学部, 准教授 (20233504)
• Co-Investigator(Kenkyū-buntansha): 貴家 康男 聖マリアンナ医科大学, 医学部, 助教 (60308450) ; 芳賀 俊明 聖マリアンナ医科大学, 医学部, 研究技術員 (80535625) ; 中野 三穂 聖マリアンナ医科大学, 医学部, 助教 (90621574)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: P糖蛋白質 / 治療抵抗性統合失調症 / クロザピン / アリピプラゾール / ジゴキシン

Outline of Final Research Achievements

P-glycoprotein (P-gp) influences the distribution of drugs across the blood-brain barrier, and is capable of transporting antipsychotic drugs such as aripiprazole and risperidone. Clozapine, which is used clinically for treatment-resistant schizophrenia, is not a P-gp substrate. C57BL/6 mice were orally administered aripiprazole, blonanserin, or clozapine at 10 mg/kg once daily for 6 weeks, and P-gp mRNA (Abcb1a/Abcb1b) and protein (Abcb1a/Abcb1b) expression levels were measured.
This is the first report that chronic aripiprazole treatment increases P-gp mRNA and protein expression in animals, which is associated with the inhibition of digoxin excretion from the brain. These results suggest that increased P-gp expression induced by aripiprazole is mediated by its interaction with P-gp.

Free Research Field

神経精神医学