Radiosynthesis of a 125 I analog of a highly selective alpha3beta4 nicotinic acetylcholine receptor antagonist ligand for use in autoradiography studies

The α 3 β 4 subtype of the nicotinic acetylcholine receptors (nAChR) is present in limited but specific areas of the brain unlike the widely distributed α 4 β 2 nAChR subtype, known to be involved in the addictive effects of nicotine. Recently, the α 3 β 4 nAChR subtype has been linked to addiction to nicotine as well as other drugs of abuse. However, there have been no subtype‐selective α 3 β 4 nAChR ligands available to study the role of this receptor in drug addiction. Our laboratory has discovered a series of very high affinity and highly selective ligands for the α 3 β 4 nAChR subtype. We now report the synthesis of a radiolabeled 125 I analog of N ‐(2‐iodophenyl)‐9‐methyl‐9‐azabicyclo[3.3.1]nonan‐3‐amine (AT‐1012), a subnanomolar affinity, highly selective α 3 β 4 nAChR ligand from this series. This analog, [ 125 I] AT‐1012, was synthesized by a facile radio‐iodination of a tributylstannylated precursor, which gave the radiolabeled compound with high specific activity and radiochemical purity. This high‐affinity radioactive α 3 β 4 nAChR antagonist is very useful as a pharmacological tool in autoradiography studies, to elucidate the localization of the α 3 β 4 nAChR in the brain and study its pharmacology in the brain reward circuit. Copyright © 2012 John Wiley & Sons, Ltd.