Stereospecific hydrolysis of 8α9α and 89epoxyhexahydrocannabinols in the mouse in vivo and in vitro

S. Narimatsu, I. Yamamoto, H. Yoshimura

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

1. After i.v. injections to the mouse, both 8α9 and 89epoxyhexahydro-cannabinols (EHHCs) were easily hydrolysed to 8$b,9αdihydroxyhexahydrocannabinol (dihydroxy-HHC) rather than 8α9dihydroxy-HHC in the liver. 2. 8,9-Dihydroxy-HHCs hydroxylated at the 2' or 3' position of a pentyl side-chain were identified in vivo as liver metabolites of the epoxides. 3. The same stereospecific hydrolysis of 8,9-EHHCs were observed in vitro using liver-microsomal fractions of mice, though both epoxides were resistant to enzymic hydrolysis. 4. Several monohydroxylated 8,9-EHHCs, together with small amounts of 8,9-dihydroxy-HHCs were identified as in vitro liver metabolites of the epoxides. These metabolites could be formed not only by epoxide hydrolase but also by a mono-oxygenase system involving cytochrome P-450. 5. The magnitude of the binding affinities of cannabinoids to cytochrome P-450 was ranked in the following order: δ8-tetrahydrocannabinol (spectral dissociation constant Ks = 9.4 μM) > 89EHHC (13.3 μM) > 8α9αEHHC (34.5 μM).

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalXenobiotica
Volume15
Issue number3
DOIs
Publication statusPublished - 1985
Externally publishedYes

Fingerprint

Liver
Hydrolysis
Epoxy Compounds
Metabolites
Cytochrome P-450 Enzyme System
Cannabinol
Epoxide Hydrolases
Oxygenases
Dronabinol
Cannabinoids
Injections
In Vitro Techniques
1 alpha,2 alpha-epoxyhexahydrocannabinol

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Stereospecific hydrolysis of 8α9α and 89epoxyhexahydrocannabinols in the mouse in vivo and in vitro. / Narimatsu, S.; Yamamoto, I.; Yoshimura, H.

In: Xenobiotica, Vol. 15, No. 3, 1985, p. 227-235.

Research output: Contribution to journalArticle

Narimatsu, S. ; Yamamoto, I. ; Yoshimura, H. / Stereospecific hydrolysis of 8α9α and 89epoxyhexahydrocannabinols in the mouse in vivo and in vitro. In: Xenobiotica. 1985 ; Vol. 15, No. 3. pp. 227-235.
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