Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol

Kazuhito Watanabe, Mayumi Arai, Shizuo Narimatsu, Ikuo Yamamoto, Hidetoshi Yoshimura

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

When cannabidiol (CBD) was incubated with hepatic microsomes of mice in the presence of an NADPH-generating system, a significant decrease of cytochrome P-450 content was observed by measuring its carbon monoxide difference spectra. The decrease of cytochrome P-450 by CBD required NADPH and molecular oxygen. The effect was partially inhibited by SKF 525-A but not by various scavengers of active oxygen species, superoxide anion, hydroxyl radical and singlet oxygen. The incubation of CBD with hepatic microsomes did not affect total heme but decreased significantly free sulfhydryl contents in the microsomes. The derivatives of CBD modified in the resorcinol moiety, CBD-monomethyl- and dimethylethers, almost lost the effect on cytochrome P-450, whereas those modified in the terpene moiety, 8,9-dihydro- and 1,2,8,9-tetrahydro-CBDs exhibited some potency to inactivate cytochrome P-450. The inactivation of cytochrome P-450 by CBD and related compounds led to the inhibition of hepatic microsomal P-nitroanisole O-demethylase and aniline hydroxylase activities. These results suggest that the resorcinol moiety of CBD plays some role in the inactivation of cytochrome P-450 by the cannabinoid.

Original languageEnglish
Pages (from-to)3371-3377
Number of pages7
JournalBiochemical Pharmacology
Volume36
Issue number20
DOIs
Publication statusPublished - Oct 15 1987
Externally publishedYes

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Cannabidiol
Metabolism
Cytochrome P-450 Enzyme System
Microsomes
NADP
Nitroanisole O-Demethylase
Liver
Aniline Hydroxylase
Proadifen
Lead compounds
Singlet Oxygen
Cannabinoids
Molecular oxygen
Terpenes
Carbon Monoxide
Heme
Superoxides
Hydroxyl Radical
Reactive Oxygen Species
Oxygen

ASJC Scopus subject areas

  • Pharmacology

Cite this

Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol. / Watanabe, Kazuhito; Arai, Mayumi; Narimatsu, Shizuo; Yamamoto, Ikuo; Yoshimura, Hidetoshi.

In: Biochemical Pharmacology, Vol. 36, No. 20, 15.10.1987, p. 3371-3377.

Research output: Contribution to journalArticle

Watanabe, K, Arai, M, Narimatsu, S, Yamamoto, I & Yoshimura, H 1987, 'Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol', Biochemical Pharmacology, vol. 36, no. 20, pp. 3371-3377. https://doi.org/10.1016/0006-2952(87)90313-3
Watanabe, Kazuhito ; Arai, Mayumi ; Narimatsu, Shizuo ; Yamamoto, Ikuo ; Yoshimura, Hidetoshi. / Self-catalyzed inactivation of cytochrome P-450 during microsomal metabolism of cannabidiol. In: Biochemical Pharmacology. 1987 ; Vol. 36, No. 20. pp. 3371-3377.
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