In vivo labeling of neuronal nicotinic acetylcholine receptors with radiolabeled isomers of norchloroepibatidine

IN VITRO binding studies have shown that epibatidine and its norchloro analogues have high affinities for the cholinergic nicotinic receptor. In this study, the in vivo binding characteristics of [H](+)norchloroepibatidine (NCEPB) and [H](-)NCEPB in mice were examined. After injection of [H](+)NCEPB, radioactivity levels in all brain regions examined increased and then decreased, with different regions accumulating different levels of radioactivity. The regional distribution of radioactivity at later times paralleled the distribution of nicotinic receptor binding in vitro. The ratio of radioactivity in the superior colliculus to that in the cerebellum, a reflection or estimate of totalnon-specific binding, was strikingly high at 8 h (about 35). Drugs known to bind to nicotinic receptors reduced [H](+)NCEPB binding, while atropine and spiperone, muscarinic and dopaminergic drugs respectively, did not. [H](-)NCEPB had a similar regional distribution to [H](+)NCEPB. Pretreatment with increasing doses of non-radioactive (-)NCEPB resulted in saturation of in vivo binding of [H](-)NCEPB. These data indicate that [H](+) and (-)NCEPB are useful in vivo binding ligands for the cholinergic nicotinic receptor.