Metabolism of n-hexyl-homologues of delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in the mouse.
n-Hexyl-delta-8-tetrahydrocannabinol (n-hexyl-delta-8-THC) and n-hexyl-delta-9-THC were synthesized by condensation of (1S)-cis-verbenol with 5-n-hexyl-1,3-dihydroxybenzene and administered intraperitoneally to male Charles-River CD-1 mice. Hepatic metabolites were isolated by solvent extraction and chromatography on Sephadex LH-20 and identified by GC/MS. Eleven metabolites were identified from n-hexyl-delta-8-THC and sixteen from n-hexyl-delta-9-THC. The pattern of metabolites was intermediate between that previously observed from the pentyl homologues and that from n-heptyl-delta-9-THC with the major biotransformation pathway being hydroxylation and oxidation at C-11. Other metabolites were mainly hydroxylated derivatives of these compounds. Metabolites containing two hydroxy groups in the side-chain were present in low concentration. These have not been observed from lower homologues but are major metabolites of n-heptyl-delta-9-THC. Compared with the metabolism of the n-pentyl homologue, there was a trend towards the production of more hydroxy metabolites at the expense of carboxylic acids, in keeping with the general reduction of oxidation observed with other homologous cannabinoids as the chain length increases.
Brown
N K
NK
University Department of Pharmacology, Oxford, UK.
Harvey
D J
DJ
D000818:Animals; D001711:Biotransformation; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice
C059174:n-hexyl-delta-8-tetrahydrocannabinol; C059175:n-hexyl-delta-9-tetrahydrocannabinol; D013759:Dronabinol