| Project/Area Number |
18390037
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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 |
Drug development chemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
OHTA Shigeru Hiroshima University, Graduate School of Biomedical Sciences, Professor (60160503)
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| Co-Investigator(Kenkyū-buntansha) |
KOTAKE Yaichiro Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (20335649)
SUGIHARA Kazumi Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor (20271067)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,760,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | parkinsonism / tetrahydroisoquinoline / P-glycoprotein / neurotxin / prodrug |
|---|
| Research Abstract |
The purpose of this research is to find anti-Parkinson's disease agent from 1-methyl-tetrahydroisoquinoline derivatives. Hydroxy derivatives have high effect, but they are difficult to penetrate of blood-brain barrier, because of their water solubility.
The ester group was introduced to the hydroxylated 1-methyl tetrahydroisoquinoline derivatives. They had better anti-parkinsonism effect than hydroxyl derivatives. The second purpose of this study is the examination of the relationship between parkinsonism and the transport characteristics (influx/outflux) of tetrahydroisoquinolines across the blood-brain barrier. At first, to examine the substrate specificity of tetrahydroisoquinolines as P-glycoprotein (P-gp) substrates.
These results indicate that 3',4'DHBnTIQ, an endogenous parkinsonism-inducing neurotoxin, is a P-gp substrate.
These results may also suggest that P-gp inactivation and/or dysfunction in the brain are closely related to the induction of Parkinson's disease.
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