SR141716A, a potent and selective antagonist of the brain cannabinoid receptor

• Published in: FEBS letters Vol. 350; no. 2; pp. 240 - 244
• Main Authors: Rinaldi-Carmona, Murielle, Barth, Francis, Héaulme, Michel, Shire, David, Calandra, Bernard, Congy, Christian, Martinez, Serge, Maruani, Jeanne, Néliat, Gervais, Caput, Daniel, Ferrara, Pascual, Soubrié, Philippe, Brelière, Jean Claude, Le Fur, Gérard
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 22-08-1994
• Subjects: Animals; Behavioural responses; Benzoxazines; Binding, Competitive; Biological Assay; Brain - drug effects; cAMP; Cannabinoid receptor; Cannabinoids - pharmacology; Cell Membrane - metabolism; CHO, chinese hamster ovary; Cyclohexanols - metabolism; i.p., intraperitoneal; i.v., intravenous; In Vitro Techniques; Mice; Morpholines - pharmacology; Naphthalenes - pharmacology; p.o., per os; Piperidines - pharmacology; Pyrazoles - pharmacology; Rats; Receptor antagonist; Receptors, Cannabinoid; Receptors, Drug - antagonists & inhibitors; Rimonabant; Tris, Tris-[hydroxymethyl]aminomethane, Δ9-THC, tetrahydrocannabinol; Receptor antagonist; i.v., intravenous; CHO, chinese hamster ovary; i.p., intraperitoneal; Cannabinoid receptor; Tris, Tris-[hydroxymethyl]aminomethane, Δ 9-THC, tetrahydrocannabinol; p.o., per os; cAMP; Behavioural responses
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)00773-X

SR141716A is the first selective and orally active antagonist of the brain cannabinoid receptor. This compound displays nanomolar affinity for the central cannabinoid receptor but is not active on the peripheral cannabinoid receptor. In vitro, SR141716A antagonises the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylyl cyclase activity in rat brain membranes. After intraperitoneal or oral administration SR141716A antagonises classical pharmacological and behavioural effects of cannabinoid receptor agonists. This compound should prove to be a powerful tool for investigating the in vivo functions of the anandamide/cannabinoid system.