title: Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain.
abstract: We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohe xyl]-phenol (CP 55,940)-, (-)11-OH-delta8-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and delta9-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [35S]GTPgammaS functional assay. The Ki values for these drugs were determined by agonist competition binding with the cannabinoid CB1 receptor antagonist [3H]N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboxamidehydrochloride ([3H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity. The rank order of efficacy was CP 55,940 > HU-210 > anandamide > delta9-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, Tucson 85724, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Burkey
authors.forename: R M
authors.initials: RM
authors.lastname: Quock
authors.forename: P
authors.initials: P
authors.lastname: Consroe
authors.forename: F J
authors.initials: FJ
authors.lastname: Ehlert
authors.forename: Y
authors.initials: Y
authors.lastname: Hosohata
authors.forename: W R
authors.initials: WR
authors.lastname: Roeske
authors.forename: H I
authors.initials: HI
authors.lastname: Yamamura
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D003511:Cyclohexanols / Q000378:metabolism / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D063388:Endocannabinoids; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D019204:GTP-Binding Proteins; C062018:HU 211; D000077285:Rimonabant; C078814:anandamide