RELATIVE EFFICACIES OF CANNABINOID CB1 RECEPTOR AGONISTS IN THE MOUSE-BRAIN

We measured 2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP 55, 940)-, (-)11-OH-Delta (8)-tetrahydrocannabinol-dimethylheptyl (HU-210) -, anandamide- and Delta(9)-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [S-35]GTPyS functional assay. The K-i values for these drugs were determined by agonist competition bind ing with the cannabinoid CB, receptor antagonist l)-4-methyl-1H-pyrazo le-3-carboxamidehydrochloride ([H-3]SR141716A). This information was u sed to calculate the efficacy for drug stimulation of G protein activi ty. The rank order of efficacy was CP 55,940 > HU-210 > anandamide > D elta(9)-tetrahydrocannabinol with the latter two drugs being partial a gonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-me diated functional responses compared with measurements of drug potency . (C) 1997 Elsevier Science B.V.