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SR141716A is an inverse agonist at the human cannabinoid CB1 receptor

https://doi.org/10.1016/S0014-2999(97)01160-6Get rights and content

Abstract

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-pyrazole-carboxamide (SR141716A) on guanosine-5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPγS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPγS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.

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Acknowledgements

This work was supported in part by grants from the Arizona Disease Control Research Commission and the National Institute of Drug Abuse.

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