1993 Fiscal Year Final Research Report Summary
Development of anti-parkinsonism agent related to endogenous amines as pharmacophore
| Project/Area Number |
03557094
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | University of Tokyo |
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Principal Investigator |
HIROBE Masaaki University of Tokyo Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20012594)
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| Co-Investigator(Kenkyū-buntansha) |
IWASAWA Yoshiro Tanabe Pharmaceutical Co., Biological Research Center, 所長
HIGUCHI Tsunehiko Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (50173159)
MASHINO Tadahiko Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (90165697)
OHTA Shigeru Faculty of Medicine, Associate Professor, 医学部, 助教授 (60160503)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Parkinson's Disease / Anti-parkinsonism agent / Tetrahydroisoquinoline derivatives |
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| Research Abstract |
It has been known for about 5 years that tetrahydroisoquinoline(TIQ) derivatives may be related to the onset of parkinsonism. TIQ and 1-methyi-1, 2, 3, 4- tetrahydroisoquinoline (1MeTIQ) are endogenous amines coexisting in the brain of many species including humans. Mareover, 1MeTIQ has a preventive effect against parkinsonism in mice.
Methyl derivative of TIQs were synthesized in preparative scale. And these pharmacological effects were investigated. From the structure-activity relationship, a methyl group attached 1 position is contributed to locomotive activity. The number of methyl groups is affected toxicity. These findings will be useful for further investigation to find out anti-parkinsonism agents.
On the way of the investigation, we found that 1-benzyl-TIQ (1BnTIQ) had very strong neurotoxic character. This compound was also an endogeneous amine in human brain. The content of 1-BnTIQ in parkinsonians is higher than control subjects. So from these data, 1BnTIQ is a very suitable candidate for parkinsonism causing substance.
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