title: Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors.
abstract: Erysodine, an erythrina alkaloid related to dihydro-beta-erythroidine, was found to be a more potent inhibitor of [3H]cytisine binding at neuronal nicotinic acetylcholine receptors but a less potent inhibitor of [125I]alpha-bungarotoxin binding at muscle-type nicotinic acetylcholine receptors than dihydro-beta-erythroidine. Erysodine was a competitive, reversible antagonist of (-)-nicotine-induced dopamine release from striatal slices and inhibited (-)-nicotine-induced 86Rb+ efflux from IMR-32 cells. Erysodine was equipotent with dihydro-beta-erythroidine in the dopamine release assay but 10-fold more potent in the 86Rb+ 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-beta-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.
mesh_terms: D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D001392:Azocines; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004079:Dihydro-beta-Erythroidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012413:Rubidium / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes; D013696:Temperature; D014316:Tritium; D014407:Tumor Cells, Cultured; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D004079:Dihydro-beta-Erythroidine; D004298:Dopamine; D018733:Nicotinic Antagonists; D011807:Quinolizines; D012413:Rubidium; D012414:Rubidium Radioisotopes; D014316:Tritium; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C097135:erysodine