| Project/Area Number |
11470513
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SAWADA Yasufumi Graduate Sch.of Pharm.Sci., KYUSHU UNIVERSITY, Prof., 大学院・薬学研究院, 教授 (80114502)
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| Co-Investigator(Kenkyū-buntansha) |
ANAI Motoaki CRC Central Research Lab., KYUSHU UNIVERSITY, Director, 中央研究所, 所長(研究職)
MAEDA Minoru Graduate Sch.of Pharm.Sci., KYUSHU UNIVERSITY, Prof., 大学院・薬学研究院, 教授 (70101178)
HIGUCHI Shun Graduate Sch.of Pharm.Sci., KYUSHU UNIVERSITY, Prof., 大学院・薬学研究院, 教授 (40218699)
TAKANAGA Hitomi Tohoku Univ., Graduate Sch.of Pharm.Sci., Associate, 大学院・薬学研究科, 助手 (20284523)
MATSUO Hirotami Graduate Sch.of Pharm.Sci., KYUSHU UNIVERSITY, Associate, 大学院・薬学研究院, 助手 (60274479)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2000: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | Parkinsonism / dopamine receptor / catalepsy / Prescription / prediction of adverse reactions |
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| Research Abstract |
i) The intensity of catalepsy and in vivo receptor occupancies for domapine D1, D2 and muscarinic acetylcholine receptors were investigated for 25 drugs in mice. The intensity of catalepsy was found to be predictable from these receptor occupancies.
ii) The relationship between structure and drug-induced parkinsonism was investigated. The diethylaminomethyl moiety was found to play an important role in the induction of parkinsonism.
iii) A case of propiverine-induced parkinsonism was found. The mechanisms underlying the induction of parkinsonism by propiverine was investigated in mice.
iv) In vitro experiments were carried out to estimate the affinities of 25 drugs for dopamine D1, D2 and muscarinic acetylcholine receptors, which were indispensable for quantitative prediction of drug-induced parkinsonism.
v) Developed was the strategy for the quantitative prediction of drug-induced parkinsonism in humans using the above results of i) and iv).
vi) The above(iv) strategy was applied to develop a computer-aided drug information system for rational prescription.
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