AM4113 is a high affinity, selective cannabinoid CB1 neutral antagonist with Ki of 0.89 nM, exhibits 100-fold selectivity over CB2 receptors. AM4113 does not change the forskolin-stimulated cAMP accumulation in CB1-transfected HEK cells up to concentrations of 10 µM. AM4113 attenuated the AM411-induced locomotor suppression (p<0.01 at 2 mg/ kg; p<0.05 at 4 mg/kg) and analgesia. AM4113 (4.0 mg/kg) alone significantly suppressed locomotor activity compared to vehicle. AM4113 suppressed food-reinforced operant responding with rats responding on fixed ratio (FR) 1 and 5 schedules of reinforcement in a dose-dependent manner, and also suppressed feeding on high-fat, high-carbohydrate, and lab chow diets.
