Conformationally constrained epibatidine analogues 20a,b and 23a,b were synthesized using a radical cyclization as the key step. Radioligand displacement assays to six defined rat nicotinic acetylcholine receptor (nAChR) subtypes showed that 20a,b bind with moderate affinities, while 23a,b have low affinities. 20a exhibits higher affinity for the beta2 containing subtype than for the beta4 containing counterpart, while 20b possesses reversed selectivity. Modeling studies suggest that the spatial distribution of the ligand's atoms around the pharmacophore elements may control their nAChR subtype selectivity.