ERYSODINE, A COMPETITIVE ANTAGONIST AT NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS

Erysodine, an erythrina alkaloid related to dihydro-beta-erythroidine, was found to be a more potent inhibitor of [H-3]cytisine binding at n euronal nicotinic acetylcholine receptors but a less potent inhibitor of [I-125]alpha-bungarotoxin binding at muscle-type nicotinic acetylch oline receptors than dihydro-beta-erythroidine. Erysodine was a compet itive, reversible antagonist of (-)-nicotine-induced dopamine release from striatal slices and inhibited (-)-nicotine-induced Rb-86(+) efflu x from IMR-32 cells. Erysodine was equipotent with dihydro-beta-erythr oidine in the dopamine release assay but 10-fold more potent in the Rb -86(+) efflux assay, suggesting differential subtype selectivity for t hese two antagonists. Erysodine, systemically administered to mice, en tered the brain and significantly attentuated nicotine's hypothermic e ffects and its anxiolytic-like effects in the elevated plus-maze test. There was greater separation between antagonist and toxic doses for e rysodine than for dihydro-beta-erythroidine, perhaps because of erysod ine's greater selectivity for neuronal receptors. In rats, erysodine p revented both the early developing decrease and the late-developing in crease 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 erysodi ne may be a useful tool in characterizing neuronal nicotinic acetylcho line receptors.