Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain

A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective alpha 9 alpha 10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of alpha 9 alpha 10 nAChRs and greater selectivity over alpha 7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain. (C) 2011 Elsevier Ltd. All rights reserved.