Neuronal nAChR stereoselectivity to non-natural epibatidine derivatives

The frog toxin epibatidine is one of the most powerful ligands of the neuro nal nicotinic receptors and derivatives show promising possibilities for la beling in positron emission tomography studies. In an attempt to reduce epi batidine toxicity, new methyl derivatives were synthesized, tested in posit ron emission tomography imaging and in electrophysiology. labeling as well as physiological experiments highlighted the differences in sensitivity of the neuronal nicotinic acetylcholine receptors between two methyl enantiome rs and the reduction in sensitivity caused by introducing the methyl group, At present, epibatidine derivatives seem the most promising compounds for in vivo labeling of neuronal nicotinic acetylcholine receptors, (C) 1999 Fe deration of European Biochemical Societies.