| Project/Area Number |
61870084
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, Chiba University |
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Principal Investigator |
YAMAZAKI Mikio Professor, Faculty of Pharmaceutical Sciences,Chiba University, 薬学部, 教授 (70089598)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Shigetoshi Assistant Faculty of Pharmaceutical Sciences,Chiba University, 薬学部, 助手 (90092064)
NAKAGAWA Masako Assoc.Prof. Faculty of Pharmaceutical Sciences,Chiba University, 薬学部, 助教授 (40009171)
HINO Tohru Professor, Faculty of Pharmaceutical Sciences,Chiba University, 薬学部, 教授 (10009160)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1986: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | epilepsy model / convulsant / fungal metabolite / 向神経性化合物 / てんかん類似症状 / フミトレモルジンC / フミトレモルジンA類似化合物 / フミトレモルジンA,B関連誘導体 |
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| Research Abstract |
Fumitremorgin A(FTA), a fungal metabolite having a potent central nervous stimulative effect, was found to cause the abnormal behayiors resembling to the eliptic convulsion to mice. The effect was suppressed with some known ant-convulsants and 2-amino-5-phosphonoheptanoic acid(APV), an agonist of the stimulants for glutamate receptor for instance for N-methyl-d-aspartate(NMDA). The finding suggested a possibility that FTA is to be used for the induction of the epilepsy model to the experimental animals, which are useful for the screening of anticonvulstants or antiepileptic reagents.
1. Syntheses of FTA-related compounds : From 6-methoxytryptophan methylether, a five cyclic compound containing indole ring was synthesized through Pictet-Spengler reaction, condensation with L-proline, dehydrogenation etc. By using this compound as a key compound, 36 FTA-related compounds were synthesized and provided as samples for the examination of the convulsive property.and the effect on the NMDA receptor.
2. Measurement of the epileptic convulsive potency : The binding potency of ^3H-glutamate, ^3H-aspartate and^3H-APVc to the P-2fraction from mouse brain was measured with and without the FTA-related coumpounds. The exhibition of abnormal behaviors in mice with and without those samples was also observed.
FTA was found conclusively to be a possible lead compound for research and development of the useful convulsant to make the epilepsy model.
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