6-(2-Phenylethyl)nicotine: A novel nicotinic cholinergic receptor ligand

6-(2-Phenylethyl)nicotine (1b; Ki = 15 nM) was unexpectedly found to bind at α4β2 nicotinic cholinergic (nACh) receptors. Although this compound failed to produce nicotine-like agonist action in several functional assays, 1b antagonized the antinociceptive effects of nicotine (mouse tail-flick assay) in a dose-dependent fashion when administered via an intrathecal route.

Defying presumed structure–affinity relationships, nicotine analog 1b (Ki = 15 nM) was unexpectedly found to bind to α4β2 nACh receptors. Administered via an intrathecal route, 1b antagonized the antinociceptive actions of (−)nicotine in the mouse tail-flick assay.Figure optionsDownload as PowerPoint slide