Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse

S. Narimatsu, K. Watanabe, T. Shimonishi, K. Matsubara, I. Yamamoto, H. Yoshimura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Metabolic disposition of 8 α, 9 α- 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 60 min 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 15 min after 8, 9-EHHCs injections increased significantly in the liver of mice pretreated with SKF 525-A (25 mg/kg, i.p.) comparing with the control. When Δ8-tetrahydrocannabinol (Δ8-THC), 8α, 9α- or 8β, 9β-EHHC was injected into mice intracerebroventricularly (25 μg/head), pentobarbital (40 mg/kg, i.p.)-induced sleep prolonging effect was ranked in the following order, 8β,9β-EHHC>Δ8-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.

Original languageEnglish
Pages (from-to)671-676
Number of pages6
JournalJournal of Pharmacobio-Dynamics
Volume7
Issue number9
Publication statusPublished - 1984
Externally publishedYes

Fingerprint

Epoxy Compounds
Dronabinol
Liver
Pharmacology
Proadifen
Epoxide Hydrolases
Brain
Pentobarbital
Mixed Function Oxygenases
Intravenous Injections
Gas Chromatography
Cytochrome P-450 Enzyme System
Sleep
Central Nervous System
Head
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Narimatsu, S., Watanabe, K., Shimonishi, T., Matsubara, K., Yamamoto, I., & Yoshimura, H. (1984). Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse. Journal of Pharmacobio-Dynamics, 7(9), 671-676.

Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse. / Narimatsu, S.; Watanabe, K.; Shimonishi, T.; Matsubara, K.; Yamamoto, I.; Yoshimura, H.

In: Journal of Pharmacobio-Dynamics, Vol. 7, No. 9, 1984, p. 671-676.

Research output: Contribution to journalArticle

Narimatsu, S, Watanabe, K, Shimonishi, T, Matsubara, K, Yamamoto, I & Yoshimura, H 1984, 'Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse', Journal of Pharmacobio-Dynamics, vol. 7, no. 9, pp. 671-676.
Narimatsu S, Watanabe K, Shimonishi T, Matsubara K, Yamamoto I, Yoshimura H. Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse. Journal of Pharmacobio-Dynamics. 1984;7(9):671-676.
Narimatsu, S. ; Watanabe, K. ; Shimonishi, T. ; Matsubara, K. ; Yamamoto, I. ; Yoshimura, H. / Metabolic disposition of 8α, 9α- and 8β, 9β-epoxyhexahydrocannabinols in the mouse. In: Journal of Pharmacobio-Dynamics. 1984 ; Vol. 7, No. 9. pp. 671-676.
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