文章基本信息

标题：大麻成分の代謝と薬理作用
本地全文：下载
作者：山本郁男 ; 吉村英敏
期刊名称：Journal of Health Science
印刷版ISSN：1344-9702
电子版ISSN：1347-5207
出版年度：1982
卷号：28
期号：5
页码：233-248
DOI：10.1248/jhs1956.28.5_233
出版社：The Pharmaceutical Society of Japan
摘要：This review is concerned primarily with our recent papers which have been published or presented since 1978. Especially, metabolic conversion of Δ⁸-THC to Δ⁸-THC-11-oic acid and to 8α, 9α-epoxyhexahydrocannabinol (8α, 9α-EHHC) and their pharmacological implications are described. Liver microsomes catalyze formation of 11-OH-Δ⁸-THC from Δ⁸-THC, 11-oxo-Δ⁸-THC from 11-OH-Δ⁸-THC, and 8α, 9α-EHHC from Δ⁸-THC. The involvement of cytochrome P-450 in these reactions were suggested in vivo as well as in vitro. 11-OH-Δ⁸-THC was detected and determined as a metabolite in vivo of Δ⁸-THC in the liver and brain of mice. 11-OH-Δ⁸-THC, when administered to mice, showed higher distribution in the brain as compared with Δ⁸-THC. Pharmacological activities of 11-OH-Δ⁸-THC, 11-oxo-Δ⁸-THC, Δ⁸-THC-11-oic acid, 8α, 9α-EHHC, 8β, 9β-EHHC, 9α, 10α-EHHC and 8β, 9α-di OH-HHC were compared with that of Δ⁸-THC using mice. Pharmacological effect of 11-OH-Δ⁸-THC, 11-oxo-Δ⁸-THC, 8β, 9β-EHHC and 9α, 10α-EHHC were more potent than that of Δ⁸-THC in the cataleptogenic, hypothermic, pentobarbital-induced sleep prolonging, and anticonvulsant effects. Daily administration of 11-OH-Δ⁸-THC or 11-oxo-Δ⁸-THC as well as Δ⁸-THC quickly induced tolerance to their hypothermic and pentobarbital-induced sleep-prolonging effects. The LD₅₀s of 11-OH-Δ⁸-THC, 11-oxo-Δ⁸-THC and Δ⁸-THC-11-oic acid are larger than that of Δ⁸-THC.
关键词：Δ8-tetrahydrocannabinol;11-hydroxy-Δ8-tetrahydrocannabinol;11-oxo-Δ8-tetrahydrocannabinol;Δ8-tetrahydrocannabinol-11-oic acid;8α, 9α-epoxyhexahydrocannabinol;8β, 9β-epoxyhexahydrocannabinol;9α, 10α-epoxyhexahydrocannabinol;8β, 9α-dihydroxyhexahydrocannabinol;in vivo and in vitro metabolism;catalepsy;hypothermic;pentobarbital-induced sleeping time;anticonvulsant effect;tolerance;LD50