METABOLIC DISPOSITION OF 8α, 9α-AND 8β, 9β-EPOXYHEXAHYDROCANNABINOLS IN THE MOUSE
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概要
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Metabolic disposition of 8α, 9α-and 8β, 9β-epoxyhexahydrocannabinols (EHHCs) was studied using mice to clarify mechanisms which cause a difference in their pharmacological activities. At given time intervals from 0.5 to 60min after intravenous injections of 8,9-EHHCs (10mg/kg), levels of unchanged epoxides extracted from blood, liver and brain of mice were determined by gas chromatography. Blood levels of both epoxides declined biphasically, and the concentrations of 8α, 9α-EHHC were higher than those of 8β, 9β-EHHC at all the time intervals determined. Biological half-lives in the slower phase were 17 and 13 min, respectively, for 8α, 9α-and 8β, 9β-EHHCs. A similar result was obtained for 8,9-EHHCs concentrations in the liver. However, no significant difference in the brain levels was found between 8α, 9α-and 8β, 9β-EHHCs. Concentrations of 8α, 9β-and 8β, 9α-dihydroxyhexahydrocannabinols as well as unchanged epoxides 15min after 8,9-EHHCs injections increased significantly in the liver of mice pretreated with SKF 525-A (25mg/kg, i.p.) comparing with the control. When Δ^8-tetrahydrocannabinol (Δ^8-THC), 8α, 9α-or 8β, 9β-EHHC was injected into mice intracerebroventricularly (25μg/head), pentobarbital (40mg/kg, i.p.)-induced sleep prolonging effect was ranked in the following order, 8β, 9β-EHHC>Δ^8-THC>8α, 9α-EHHC. These results suggest that monooxygenase system involving cytochrome P-450 and epoxide hydrolase together play important roles in the epoxides metabolism. In addition, different activities of 8α, 9α-and 8β, 9β-EHHCs to the central nervous system may cause a difference in their pharmacological effects rather than metabolic factors.
- 社団法人日本薬学会の論文
著者
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中村 紳一郎
Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.
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YAMAMOTO IKUO
Department of Laboratory Medicine, Miyazaki Medical College
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Watanabe Kazuhito
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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YOSHIMURA Hidetoshi
Department of Food and Nutrition, Nakamura Gakuen University
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Yamamoto Ikuo
北陸大学 薬 衛化
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Yamamoto Ikuo
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Nakamura S
Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.
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NARIMATSU SHIZUO
Departments of Hygienic Chemistry
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SHIMONISHI TATSUYUKI
Department of Hygienic Chemistry, School of Pharmacy, Hokuriku University
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MATSUBARA KAZUHIKO
Department of Hygienic Chemistry, School of Pharmacy, Hokuriku University
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Nakamura Satoko
Osaka University Of Pharmaceutical Sciences
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Watanabe Kazuhito
Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University
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Yoshimura Hidetoshi
Department Of Food And Nutrition Nakamura Gakuen University
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Narimatsu Shizuo
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Watanabe Kazuhito
Faculty Of Pharmaceutical Sciences Kyushu University
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Matsubara Kazuhiko
School Of Pharmacy Hokuriku University
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Yoshimura Hidetoshi
Department Of Food And Nutrition Nakamura Gakuen
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Yamamoto Ikuo
Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University
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Shimonishi Tatsuyuki
School Of Pharmacy Hokuriku University
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