title: A novel metabolite, an oxepin formed from cannabidiol with guinea-pig hepatic microsomes.
abstract: The metabolic formation of an oxepin derivative, 3-pentyl-6,7,7a,8,9,11a-hexahydro-1,7-dihydroxy-7,10- dimethyldibenzo-[b,d]-oxepin, from cannabidiol was studied in-vitro using guinea-pig hepatic microsomes. The hepatic microsomes catalysed the formation of the metabolite from cannabidiol and 8S, 9-epoxycannabidiol in the presence of an NADPH-generating system and 3, 3, 3-trichloropropene-1, 2-oxide. 8S, 9-Epoxycannabidiol was thought to be an intermediate in the formation of the metabolite, which was identified by gas chromatography-mass spectrometry. The metabolite synthesized from 8S, 9-epoxycannabidiol diacetate exhibited catalepsy, hypothermia and pentobarbitone-induced sleep prolongation in mice, although the pharmacological effect was less potent than that of delta 9-tetrahydrocannabinol.
authors.affiliation: Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Matsunaga
authors.forename: H
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000378:metabolism* / Q000494:pharmacology; D002375:Catalepsy / Q000188:drug therapy*; D003990:Dibenzoxepins / Q000378:metabolism / Q000494:pharmacology; D013759:Dronabinol / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D007035:Hypothermia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010082:Oxepins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012890:Sleep / Q000187:drug effects
chemical_list: D003990:Dibenzoxepins; D010082:Oxepins; C098139:3-pentyl-6,7,7a,8,9,11a-hexahydro-1,7-dihydroxy-7,10-dimethyldibenzo(b,d)oxepin; D002185:Cannabidiol; D013759:Dronabinol