JN403, in vitro characterization of a novel nicotinic acetylcholine receptor α7 selective agonist

Abstract

This report describes the in vitro features of a novel selective nicotinic acetylcholine receptor (nAChR) α7 agonist, JN403, (S)-(1-Aza-bicyclo[2.2.2]oct-3-yl)-carbamic acid (S)-1-(2-fluoro-phenyl)-ethyl ester. JN403 was evaluated in a number of in vitro systems of different species, at recombinant receptors using radioligand binding, signal transduction and electrophysiological studies. When using [125I] α-bungarotoxin (α-BTX) as a radioligand, JN403 has high affinity for human recombinant nAChR α7 (pKD = 6.7). Functionally, JN403 is a partial and potent agonist at human nAChR α7. The compound stimulates calcium influx in GH3 cells recombinantly expressing the human nAChR with an pEC50 of 7..