Peripherally-restricted cannabinoid receptor 1 (CB₁) selective antagonists have the potential to inhibit food intake while also escaping centrally-mediated neuropsychiatric side effects. AM6545 is a novel CB₁ selective neutral antagonist with low CNS penetration, exhibiting K_i values of 1.7 and 523 nM for CB₁ and CB₂ receptors, respectively.¹ It reduces food intake and food-reinforced behavior, such as time spent feeding, in a dose-dependent manner, resulting in decreased body weight.^1,2 AM6545 produces improvements in glucose homeostasis, fatty liver, and plasma lipid profiles in mice with diet-induced obesity.³ It does not affect behavior responses that are associated with activation of CB₁ receptors in the brain.³

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1.Cluny, N.L.,Vemuri, V.K.,Chambers, A.P., et al. A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. British Journal of Pharmacology 161(3), 629-642 (2010).

2.Randall, P.A.,Vemuri, V.K.,Segovia, K.N., et al. The novel cannabinoid CB₁ antagonist AM6545 suppresses food intake and food-reinforced behavior. Pharmacology, Biochemistry, and Behavior 97(1), 179-184 (2010).

3.Tam, J.,Vemuri, V.K.,Liu, J., et al. Peripheral CB₁ cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. Journal of Clinical Investigation 120(8), 2953-2966 (2010).