Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes

Life Sciences

Volumn 80, Issue 15, 2007, Pages 1415-1419

  Watanabe, Kazuhito ^a   Yamaori, Satoshi ^a   Funahashi, Tatsuya ^a   Kimura, Toshiyuki ^a   Yamamoto, Ikuo ^b  

^a HOKURIKU UNIVERSITY   (Japan)

^b KYUSHU UNIVERSITY OF HEALTH AND WELFARE   (Japan)

Author keywords

Cannabinol; CYP2C9; CYP3A4; Human hepatic microsomes; Oxidative metabolism; Tetrahydrocannabinol

Indexed keywords

11 HYDROXYCANNABINOL; 8 HYDROXYCANNABINOL; ARGININE; CANNABINOID; CANNABINOL; CANNABINOL DERIVATIVE; CYTOCHROME P450; CYTOCHROME P450 2C; CYTOCHROME P450 2C9; CYTOCHROME P450 3A; CYTOCHROME P450 3A4; DELTA8 TETRAHYDROCANNABINOL; DRONABINOL; KETOCONAZOLE; SULFAPHENAZOLE; TETRAHYDROCANNABINOL; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CONTROLLED STUDY; DAUDI CELL; ENZYME METABOLISM; EPOXIDATION; HUMAN; HUMAN CELL; HYDROXYLATION; LIVER MICROSOME; OXIDATION; PROTEIN EXPRESSION;

ARYL HYDROCARBON HYDROXYLASES; B-LYMPHOCYTES; CANNABINOL; CATALYSIS; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; HUMANS; HYDROXYLATION; MICROSOMES, LIVER; TETRAHYDROCANNABINOL;

EID: 33847633815     PISSN: 00243205     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.lfs.2006.12.032     Document Type: Article

References (30)

1. 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacological Reviews 38 (1986) 21-43
2. Aramaki H., Tomiyasu N., Yoshimura H., and Tsukamoto H. Forensic chemical study on marihuana. I. A detection method of the principal constituents by thin-layer and gas chromatographies. Chemical and Pharmaceutical Bulletin 16 (1968) 822-826
3. Baldwin S.J., Bloomer J.C., Smith G.J., Ayrton A.D., Clarke S.E., and Chenery R.J. Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9. Xenobiotica 25 (1995) 261-270
4. Bland T.M., Haining R.L., Tracy T.S., and Callery P.S. CYP2C-catalyzed delta(9)-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin. Biochemical Pharmacology 70 (2005) 1096-1103
5. 1-tetrahydrocannabinol. Drug Metabolism and Disposition 20 (1992) 241-246
6. Emoto C., Yamazaki H., Iketani H., Yamasaki S., Satoh T., Shimizu R., Suzuki S., Shimada N., Nakajima M., and Yokoi T. Cooperativity of α-naphthoflavone in cytochrome P4503A-dependent drug oxidation activities in hepatic microsomes from mouse and human. Xenobiotica 31 (2001) 265-275
7. 8-tetrahydrocannabinol in monkey liver microsomes. Drug Metabolism and Pharmacokinetics 20 (2005) 358-367
8. Gaoni Y., and Mechoulam R. Hashish-VII, the isomerization of cannabidiol to tetrahydrocannabinols. Tetrahedron 22 (1966) 1481-1488
9. 1-tetrahydrocannabinol formed by human liver. Drug Metabolism and Disposition 10 (1982) 297-301
10. Harvey D.J. Chemistry, metabolism, and pharmacokinetics of the cannabinoids. In: Nahas G.G. (Ed). Marihuana in Science and Medicine (1984), Raven Press, New York 37-107
11. 6-tetrahydrocannabinol with selenium dioxide. Chemical and Pharmaceutical Bulletin 22 (1974) 1519-1525
12. Lowry O.H., Rosebrough N.J., Farr A.L., and Randall R.J. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193 (1951) 265-275
13. Mechoulam R., Varconi H., Ben-Zvi Z., Edery H., and Grunfeld Y. Synthesis and biological activity of five tetrahydrocannabinol metabolites. Journal of American Chemical Society 94 (1972) 7930-7931
14. 9-tetrahydrocannabinol by liver microsomes of phenobarbital-treated mice and its pharmacological activities in mice. Journal of Pharmacobio-Dynamics 6 (1983) 558-564
15. 9-tetrahydrocannabinol by rat liver microsomes. Drug Metabolism and Disposition 18 (1990) 943-948
16. 9-tetrahydrocannabinol in the rat. Biochemical Pharmacology 41 (1991) 1187-1194
17. Newton D.J., Wang R.W., and Lu A.Y.H. Cytochrome P450 inhibitors, evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metabolism and Disposition 23 (1995) 154-158
18. 6-tetrahydrocannabinol metabolite. Acta Pharmaceutica Suecica 16 (1979) 21-33
19. Ono S., Hatanaka T., Hotta H., Satoh T., Gonzalez F.J., and Tsutsui M. Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 26 (1996) 681-693
20. 9-tetrahydrocannabinol. Journal of American Chemical Society 97 (1975) 3798-3802
21. Schwab G.E., Raucy J.L., and Johnson E.F. Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by α-naphthoflavone. Molecular Pharmacology 33 (1988) 493-499
22. 8-tetrahydrocannabinol and its metabolites oxidized at 11-position. European Journal of Pharmacology 63 (1980) 1-6
23. 8-tetrahydrocannabinol, on the hepatic microsomal drug-metabolizing enzyme system of mice. Biochemical Pharmacology 35 (1986) 1861-1865
24. Watanabe K., Narimatsu S., Matsunaga T., Yamamoto I., and Yoshimura H. A cytochrome P450 isozyme having aldehyde oxygenase activity plays a major role in metabolizing cannabinoids by mouse hepatic microsomes. Biochemical Pharmacology 46 (1993) 405-411
25. Watanabe K., Matsunaga T., Yamamoto I., Funae Y., and Yoshimura H. Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman. Biological and Pharmaceutical Bulletin 18 (1995) 1138-1141
26. Watanabe K., Yamaori S., Funahashi T., Kimura T., and Yamamoto I. 8-Hydroxycannabinol, a new metabolite of cannabinol formed by human hepatic microsomes. Forensic Toxicology 24 (2006) 80-82
27. 8-tetrahydrocannabinol. Chemical and Pharmaceutical Bulletin 31 (1983) 1784-1787
28. Yamamoto I., Watanabe K., Kuzuoka K., Narimatsu S., and Yoshimura H. The pharmacological activity of cannabinol and its major metabolite, 11-hydroxycannabinol. Chemical and Pharmaceutical Bulletin 35 (1987) 2144-2147
29. Yamamoto I., Watanabe K., Narimatsu S., and Yoshimura H. Recent advances in the metabolism of cannabinoids. International Journal of Biochemistry and Cell Biology 27 (1995) 741-746
30. Yamamoto I., Watanabe K., Matsunaga T., Kimura T., Funahashi T., and Yoshimura H. Pharmacology and toxicology of marijuana - on the metabolic activation of cannabinoids and its mechanism. Journal of Toxicology. Toxin Reviews 22 (2003) 577-589