Abstract
Defying presumed structure–affinity relationships, nicotine analog
1b (
K
i
=
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.
6-(2-Phenylethyl)nicotine (
1b;
K
i
=
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.