| Project/Area Number |
14370718
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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 |
Chemical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
TAKAYAMA Hiromitsu Chiba University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (90171561)
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| Co-Investigator(Kenkyū-buntansha) |
MURAYAMA Toshihiko Chiba University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (90174317)
HORIE Shunji Chiba University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究院, 助教授 (50209285)
相見 則郎 千葉大学, 大学院・薬学研究院, 教授 (30009170)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Mitrapyna speciosa / indole alkaloid / analgesic activity / opioid / structure-activity relationship / chemical modification / agonist / antinociceptive activity / プロドラッグ / オピオイド受容体 / ピロリジノインドリン / Mitragyna africanus |
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| Research Abstract |
The leaves of a tropical plant, Mitragyna speciosa Korth (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M.speciosa, was found to exhibit potent antinociceptive activity in mice.
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