AM251

AM251 is a cannabinoid 1 (CB1) receptor 1 antagonist.{9721} It binds to CB1 receptors in rat forebrain membrane preparations (Ki = 7.5 nM) and is selective over CB2 receptors in mouse spleen preparations (Ki = 2,290 nM) in radioligand binding assays. AM251 inhibits GTPyS binding induced by the CB receptor agonist CP 55,940 in HEK293 cells expressing human CB1 receptors (EC50 = 8 nM).{17583} AM251 (10 mg/kg) decreases immobility time in the forced swim test in wild-type but not CB1 receptor-deficient mice.{38334} It reduces fasting-induced food intake and body weight gain in mice when administered at a dose of 30 mg/kg. AM251 also induces GTPyS binding in HEK293 cells expressing the orphan receptor GPR55 (EC50 = 39 nM) and potentiates GABA-induced GABAA receptor currents (EC50 = 0.4 µM).{17583,38332} It prevents TGF-B1-induced epithelial-to-mesenchymal transition (EMT), inhibits SMAD2/3 and p38 MAPK activation, and reduces the expression of EMT-related transcription factors in HK-2 renal tubule epithelial cells.{38335} AM251 induces cell cycle arrest at the G2/M phase and apoptosis in A375 human melanoma cells.{38333}