2-[F]Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine

Neuronal nicotinic cholinergic receptors (nAChRs) are a heterogeneous family of ligand-gated ion channels expressed in the central nervous system, where their activation by acetylcholine and nicotine always causes a rapid increase in cellular permeability to ions, such as Na and Ca (1-3). Nicotinic receptors exist as pentamers (homomeric or heteromeric) in various brain regions and ganglia. There are nine subtypes of ligand-binding α (α2-α10) and four subtypes of structural β (β2-β5). nAChRs have been demonstrated to be involved in cognitive processes such as learning and memory and control of movement in normal subjects. Dysfunction of nAChR has been implicated to a number of human diseases such as schizophrenia, Huntington's disease, Alzheimer's disease (AD) and Parkinson's disease. nAChRs also play a significant role in nicotine addiction and related health problems associated with tobacco smoking. 3-[2(S)-2-azetidinylmethoxy]pyridine (A-85380) is a highly potent and selective α4β2 nAChR agonist with subnanomolar affinity (4). A-85380 has been labeled as 2-[F]Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[F]fluoro-A-85380) (5). 2-[F]fluoro-A-85380 (2-[F]FA) is being developed as a positron emission tomography (PET) agent for the non-invasive study of nAChR in the brain.