IN VIVO EFFECTS OF TETRAHYDROCANNABINOLS AND THEIR EIGHT MONOOXYGENATED METABOLITES ON THE HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEMS OF MICE
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概要
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In vivo effects of tetrahydrocannabinols (THCs) and their eight monooxygenated metabolites on the hepatic microsomal drug-metabolizing enzymes in mice were studied. Δ^8-THC and its metabolites (7α-hydroxy-, 7β-hydroxy- and 7-oxo-Δ^8-THC, and 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinol) tended to increase the enzyme contents or activities except for 7β-hydroxy-Δ^8-THC which affected the microsomal enzymes in a different manner between the single and subchronic treatments. Single administration (5 mg/kg, i.v.) of 7-oxo-Δ^8-THC, 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinol led to a significant increase in hepatic microsomal p-nitroanisole O-demethylase and aniline hydroxylase activities accompanying a significant increase in cytochrome P-450 content in hepatic microsomes. The same results were obtained with subchronic treatment of mice with these metabolites (5 mg/kg/d, i.v. for 7 d), although the effect of 8β, 9β-epoxyhexahydrocannabinol on cytochrome P-450 was not statistically significant. 7β-Hydroxy-Δ^8-THC significantly increased nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome creductase and aniline hydroxylase activities by single administration, while the metabolite significantly decreased the contents of cytochrome b_5 and P-450 and p-nitrophenol uridine diphosphate-glucuronyltransferase activity by the subchronic treatment. In contrast, Δ^9-THC and its metabolites (8α-hydroxy-, 8β-hydroxy- and 8-oxo-Δ^9-THC) did not significantly affect the microsomal enzymes by both treatments except that the single administration of 8α-hydroxy-Δ^9-THC and the subchronic treatment of Δ^9-THC significantly decreased NADPH-cytochrome c reductase activity. These results indicated that monooxygenated metabolites of Δ^8- and Δ^9-THC affect the hepatic microsomal drug-metabolizing enzyme systems of mice differently.
- 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
School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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Yamamoto Ikuo
北陸大学 薬 衛化
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Nakamura S
Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.
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WATANABE KAZUHITO
School of Pharmacy, Hokuriku University
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NARIMATSU SHIZUO
School of Pharmacy, Hokuriku University
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ARAI MAYUMI
School of Pharmacy, Hokuriku University
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YOSHIMURA HIDETOSHI
School of Pharmacy, Hokuriku University
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Nakamura Satoko
Osaka University Of Pharmaceutical Sciences
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Arai Mayumi
School Of Pharmacy Hokuriku University:faculty Of Pharmaceutical Sciences Kyushu University
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Nakamura S
Laboratories Of Health Chemistry Graduate School Of Medicine Dentistry And Pharmaceutical Sciences O
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Watanabe Kazuhito
Faculty Of Pharmaceutical Sciences Kyushu University
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Yamamoto Ikuo
School Of Pharmaceutical Sciences Kyushu University Of Health And Welfare
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