AM6545 is a selective and potent peripheral restricted cannabinoid receptor 1 (CB1) antagonist that inhibits the CB2 receptor, ameliorates hypometabolic obesity and improves adipokine secretion in monosodium glutamate-induced obese mice, and may be useful in the study of obesity and diabetes.

METHODS: AM6545 (0.5 mM) was used to treat 3T3-L1 adipocytes to examine possible beiging effects of peripheral CB1R antagonist treatment, and the expression of key beiging markers was examined.
RESULTS: AM6545 significantly increased many genes involved in adipocyte coagulation, including peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgc1α), PR domain containing 16 (Prdm16), and uncoupling protein 1 (Ucp1), cell death-inducing DNA fragmentation factor α-like effector A (Cieda), long-chain fatty acid protein 3 (Elovl3), tumor necrosis factor receptor superfamily member 9 (Cd137), T-box transcription factor ( Tbx1), transmembrane protein 26 (Tmem26), cbp/p300 interacting transactivator 1, fibroid/endoplasmic reticulum calcium 2+-ATPase 2b (Serca2b), ryanodine receptor 2 (Ryr2). [2]

METHODS: AM6545 (1 mg/kg, intraperitoneal injection) and CNO (3 mg/kg) were administered to mice, and the discrimination index values ​​of NORT in the vagus nerve were observed 48 hours after administration.
RESULTS: AM6545 can improve memory consolidation through an adrenergic mechanism involving vagal afferent nerves. [1]