Abstract
Drugs typically used to treat pain are limited by their undesirable side effects, which has prompted a search for mechanistically different analgesic agents. We report the antinociception effect of the spirocyclopiperazinium compound LXM-10 via activation of peripheral α7 nicotinic and muscarinic acetylcholine receptors in mice. This effect was attenuated by hexamethonium, atropine methylnitrate, methyllycaconitine citrate, tropicamide, bicuculline, and phaclofen. Competition receptor-binding assays in vitro showed that LXM-10 binds with high affinity α7 nAchR and with low affinity M4 receptors. Our findings show that the antinociception signaling pathway of LXM-10 underlies activation of peripheral α7 nicotinic and possibly of M4 muscarinic receptors, which activate GABA A and GABA B receptors, resulting in antinociceptive effects without obvious side effects.
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