AM 2389

AM-2389 is a classical cannabinoid derivative which acts as a potent and reasonably selective agonist for the CB₁ receptor, with a K_i of 0.16 nM, and 26x selectivity over the related CB₂ receptor. It has high potency in animal tests of cannabinoid activity, and a medium duration of action. Replacing the 1',1'-dimethyl substitution of the dimethylheptyl side chain of classical cannabinoids with cyclopropyl or cyclopentyl results in higher potency than cyclobutyl, but only the cyclobutyl derivatives show selectivity for CB₁ over CB₂. High selectivity for CB₁ over CB₂ is difficult to achieve (cf. AM-906, AM-1235), as almost all commonly used CB₁ agonists have similar or greater affinity for CB₂ than CB₁, and the only truly highly selective CB₁ agonists known as of 2012 are eicosanoid derivatives such as O-1812.