title: Stereochemical effects of 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor.
abstract: The recent preparation of the enantiomers of 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl (THC-DMH), recrystallized to absolute enantiomeric purity, has made it possible to examine the requirement for stereospecificity for the interaction of this component with the cannabinoid receptor, defined by the binding of [3H]CP-55,940 and the adenylate cyclase enzyme. The enantiomer (-)11-OH-delta 8-THC-DMH exhibited a fully efficacious and potent (IC50 = 1.8 nM) inhibition of the accumulation of cAMP in intact N18TG2 cells. The (-)enantiomer was as efficacious and potent (Kinh = 7.2 nM) as desacetyllevonantradol in inhibiting adenylate cyclase activity in membrane preparations. The (-)enantiomer was able to compete fully for the specific binding of [3H]CP-55,940 to membranes from the brain of the rat in homologous displacement studies (Ki = 234 pM). The potency ratios exhibited by the (-) to (+)enantiomers of 11-OH-delta 8-THC-DMH exceeded 1000 for each of these activities.
authors.affiliation: Department of Pharmacology, St Louis University School of Medicine, Missouri 63104.
authors.forename: A C
authors.initials: AC
authors.lastname: Howlett
authors.forename: T M
authors.initials: TM
authors.lastname: Champion
authors.forename: G H
authors.initials: GH
authors.lastname: Wilken
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003511:Cyclohexanols / Q000378:metabolism; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C062018:HU 211