PSNCBAM-1

PSNCBAM-1 is a small molecule **negative allosteric modulator** and non-competitive antagonist of the **cannabinoid CB1 receptor**. It binds selectively to the CB1 receptor at an allosteric (non-orthosteric) site, distinct from the primary ligand-binding pocket. PSNCBAM-1 blocks the effects of CB1 agonists like CP55,940, WIN55,212-2, anandamide, and 2-arachidonoyl glycerol, but does not affect CB2 receptors. It decreases food intake and body weight in animal models, indicating potential for treatment of obesity and possibly central nervous system disorders. Mechanistically, PSNCBAM-1 demonstrates biased signaling via β-arrestin 1, inhibits agonist-induced G-protein coupling at CB1, and enhances the binding of orthosteric CB1 agonists in binding assays without causing agonist activity itself[1][2][3][4][5][7][8].