| Project/Area Number |
25461742
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
kenichi osada 聖マリアンナ医科大学, 医学部, 准教授 (20233504)
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| 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)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / P糖タンパク質 / Ｐ糖タンパク質 / ブロナンセリン |
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| 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.
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