SR141716A is an inverse agonist at the human cannabinoid CB1 receptor

The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4- benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR141716A) on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPgammaS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPgammaS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.