[I-125/123] 5-Iodo-3-pyridyl ethers: syntheses and binding to neuronal nicotinic acetylcholine receptors

Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-meth oxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-meth oxy]pyridine (5-todo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-me thoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and the ir ability to label high-affinity brain nicotinic acetylcholine receptors ( nAChRs) was evaluated. The most promising ligand, [I-123/125] 5-iodo-A-8586 5, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [I -123] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands. (C) 2001 Else vier Science Inc. All rights reserved.