AM 1220

AM-1220 is a drug that acts as a potent and moderately selective agonist for the cannabinoid receptor CB₁, with around 19x selectivity for CB₁ over the related CB₂ receptor. It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop, but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two enantiomers with quite different potency, the (R) enantiomer having a K_i of 0.27nM at CB₁ while the (S) enantiomer has a much weaker K_i of 217nM. A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or other groups, or the 1-(N-methylpiperidin-2-ylmethyl) group replaced by similar heterocyclic groups such as N-methylpyrrolidin-2-ylmethyl or N-methylmorpholin-3-ylmethyl. AM-1220 was first detected as an ingredient of synthetic cannabis smoking blends in 2010.