Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors

Abstract Erysodine, an erythrina alkaloid related to dihydro-β-erythroidine, was found to be a more potent inhibitor of [ 3 H]cytisine binding at neuronal nicotinic acetylcholine receptors but a less potent inhibitor of [ 125 I]α-bungarotoxin binding at muscle-type nicotinic acetylcholine receptors than dihydro-β-erythroidine. Erysodine was a competitive, reversible antagonist of (−)-nicotine-induced dopamine release from striatal slices and inhibited (−)-nicotine-induced 86 Rb + efflux from IMR-32 cells. Erysodine was equipotent with dihydro-β-erythroidine in the dopamine release assay but 10-fold more potent in the 86 Rb + efflux assay, suggesting differential subtype selectivity for these two antagonists. Erysodine, systemically administered to mice, entered the brain and significantly attentuated nicotine's hypothermic effects and its anxiolytic-like effects in the elevated plus-maze test. There was greater separation between antagonist and toxic doses for erysodine than for dihydro-β-erythroidine, perhaps because of erysodine's greater selectivity for neuronal receptors. In rats, erysodine prevented both the early developing decrease and the late-developing increase in locomotor activity produced by (−)-nicotine. The potent and competitive nature of erysodine's antagonism together with its ability to enter the brain after systemic administration suggest that erysodine may be a useful tool in characterizing neuronal nicotinic acetylcholine receptors.