AM6538

**AM6538** is a synthetic small molecule and structural analog of rimonabant that acts as a high-affinity, long-acting, pseudo-irreversible **cannabinoid CB1 receptor antagonist**. It binds to CB1 receptors in a wash-resistant manner, stabilizing the receptor for crystallographic studies, with a solved crystal structure of human CB1 in complex with AM6538 at 2.8 Å resolution. Developed primarily as a research tool by the laboratory of Alexandros Makriyannis at Northeastern University, it demonstrates prolonged in vivo antagonism in mice and squirrel monkeys, blocking cannabinoid agonist effects (e.g., antinociception, discriminative stimulus) for up to 7 days after a single dose due to tight binding and reduced receptor availability. It has been used to probe ligand efficacy differences among agonists like THC, WIN 55,212, and AM4054, but lacks reported clinical development or therapeutic indications.

Other names

4-(4-(1-(2,4-dichlorophenyl)-4-methyl-3-(piperidin-1-ylcarbamoyl)-1H-pyrazol-5-yl)phenyl)but-3-ynyl nitratecompound 10compound10compound-10Example 2Example2Example-2