Novel Alpha 3 Beta 4 Nicotinic Acetylcholine Receptor-Selective Ligands. Discovery, Structure-Activity Studies, and Pharmacological Evaluation

Abstract

Antagonist activity at the α3β4 nicotinic acetylcholine receptor (nAChR) is thought to contribute to the antiaddictive properties of several compounds. However, truly selective ligands for the α3β4 nAChR have not been available. We report the discovery and SAR of a novel class of compounds that bind to the α3β4 nAChR and have no measurable affinity for the α4β2 or α7 subtype. In functional assays the lead compound antagonized epibatidine-induced Ca²⁺ flux in α3β4-transfected cells in a noncompetitive manner