title: SR141716A is an inverse agonist at the human cannabinoid CB1 receptor.
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-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.
authors.affiliation: Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Landsman
authors.forename: T H
authors.initials: TH
authors.lastname: Burkey
authors.forename: P
authors.initials: P
authors.lastname: Consroe
authors.forename: W R
authors.initials: WR
authors.lastname: Roeske
authors.forename: H I
authors.initials: HI
authors.lastname: Yamamura
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines; D001667:Binding, Competitive; D016466:CHO Cells / Q000187:drug effects; D006224:Cricetinae; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D014162:Transfection
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant