Epibatidine analogues as selective ligands for the αxβ2-containing subtypes of nicotinic acetylcholine receptors

A series of epibatidine analogues was synthesized and characterized in vitro. These compounds are high affinity ligands for the nicotinic acetylcholine receptors (nAChR). They display binding selectivity for the αxβ2 subtypes of nAChRs over the αxβ4 subtypes, and especially for the α4β2 and α2β2 subtypes. Furthermore, most of these new nicotinic compounds display little, if any, agonist activities at α3β4 nAChR. As a result they might become lead structures for the design and synthesis of highly selective ligands for nAChR subtypes containing the β2 subunit.