AM6545

AM6545 is a highly selective, brain-free (peripherally active) CB1 receptor antagonist (K_i=1.7 nM). AM6545 inhibits endocannabinoid signaling by competitively antagonizing CB1 receptors, inhibiting CB1-mediated appetite stimulation and inflammatory responses without affecting cAMP levels. AM6545 significantly reduces food intake and body weight in mice, while improving metabolic syndrome-related renal impairment (such as proteinuria, fibrosis) and insulin resistance. AM6545 can be used in the study of obesity and its complications^[1][2][3]. In Vitro:AM6545 (3 μM; cAMP assay) does not affect forskolin (HY-15371)-induced cAMP levels in HEK293 cells, exhibiting neutral antagonist properties^[1]. In Vivo:AM6545 (5-20 mg/kg; i.p.; once daily; 7 days or single dose) reduces food intake and sustaines body weight in Sprague Dawley rats at 10 and 20 mg/kg when treated chronically or acutely^[1].
AM6545 (10 mg/kg; ip; single dose) treatment of C57BL/6 J mice specifically induces PKA signaling activation in adipose tissue and upregulated Akt-mTOR and ERK phosphorylation levels^[2].
AM6545 (10 mg/kg; i.p.; once daily; 4 weeks) significantly improves renal function, inhibited proteinuria, uric acid excretion and renal fibrosis in a rat model of metabolic syndrome^[3].