In vivo metabolism of the n-propyl homologues of delta-8- and delta-9-tetrahydrocannabinol in the mouse.
n-Propyl-delta-8-tetrahydrocannabinol (n-propyl-delta-8-THC and n-propyl-delta-9-THC were synthesized by condensation of (1S)-cis-verbenol with 5-n-propyl-1,3-dihydroxybenzene and administered to male Charles River CD-1 mice. Hepatic metabolites were isolated by solvent extraction and chromatography on Sephadex LH-20 and identified by gas chromatography/mass spectrometry. Seven metabolites were identified from each cannabinoid. Metabolism was similar to that previously observed from the penyl homologues, with the major biotransformation pathway being the production of 11-hydroxy-propyl-THCs and their oxidation to carboxylic acid metabolites. Other metabolites were mainly hydroxylated derivatives of these compounds and the corresponding 11-alcohol. Less hydroxylation at C(8) was found with n-propyl-delta-9-THC than with the pentyl homologue, and the monohydroxy metabolite, 8-alpha-hydroxy-n-propyl-delta-9-THC, was not observed, even though it was a prominent metabolite from delta-9-THC itself. Hydroxylation occurred in the side-chain at C(2').
Brown
N K
NK
University Department of Pharmacology, Oxford, UK.
Harvey
D J
DJ
D000535:Aluminum; D017607:Aluminum Compounds; D000818:Animals; D001711:Biotransformation; D003903:Deuterium; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008094:Lithium; D018020:Lithium Compounds; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D014297:Trimethylsilyl Compounds
D017607:Aluminum Compounds; D018020:Lithium Compounds; D014297:Trimethylsilyl Compounds; C056265:propyl-delta(8)-tetrahydrocannabinol; C035731:delta-8-tetrahydrocannabinol; C042073:lithium aluminum hydride; D013759:Dronabinol; D008094:Lithium; D003903:Deuterium; D000535:Aluminum