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Development of New Type of Potent Opioid Agonists and the Molecular Mechanism for Exhibiting their Analgesic Activity

新型强效阿片受体激动剂的开发及其镇痛活性的分子机制

基本信息

批准号：
14370718
负责人：
TAKAYAMA Hiromitsu
金额：
$ 8.13万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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.

一种热带植物的叶子，美帽菊（茜草科），传统上被用作鸦片的替代品。对生长在泰国和马来西亚的植物成分的植物化学研究已经导致分离出几种9-甲氧基-Corynanthe型单萜吲哚生物碱，包括新的天然产物。新化合物的结构通过光谱和/或合成方法进行了鉴定。在体内外实验中发现了该植物的主要成分mitragynine及其类似物的强阿片激动活性，并阐明了其镇痛活性的机制。mitragynines的基本结构特征，这不同于那些吗啡和负责的镇痛活性，阐明了天然和合成衍生物的药理学评价。在mitragynine衍生物中，7-hydroxymitragynine，一种小的成分，被发现在小鼠中表现出有效的抗伤害感受活性。

项目成果

期刊论文数量（58）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A New 9-Methoxyyohimbine-Type Alkaloid from Mitragyna africanus.

来自非洲帽柱藻的新 9-甲氧基育亨宾型生物碱。

DOI：
发表时间：
2004
期刊：
Chem.Pharm.Bull. 52・3
影响因子：
0
作者：
Kikuchi;K.・Fukuda;K.・Hasegawa;T.;et. al.;日高雄二;土屋渉・久野敦・河原林裕・長谷川典巳;N.Kogure et al.;H.Takayama et al.;土屋渉・久野敦・長谷川典巳;M.Mikajima et al.;K.Katakawa et al.;H.Takayama et al.;M.Kitajima et al.;H.Takayama et al.;H.Takayama et al.
通讯作者：
H.Takayama et al.

Structure elucidation and synthesis of lycoposerramine-B, an oxime-containing Lycopodium alkaloid from Lycopodium serratum

锯叶石松中含肟的石松生物碱 lycoposrramine-B 的结构解析和合成