4-[Br]Bromophenyl-1,4-diazabicyclo(3.2.2) nonane-4-carboxylate

Neuronal α4β2 nicotinic cholinergic receptors (nAChRs) are part of a heterogeneous family of ligand-gated ion channels expressed in the central nervous system, where their activation by acetylcholine and nicotine 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 receptors (α2 to α10) and four subtypes of structural β receptors (β2 to β5). nAChRs have been found to be involved in cognitive processes such as learning memory and control of movement in normal subjects. nAChR dysfunction has been implicated in a number of human diseases such as schizophrenia, Huntington's disease, Alzheimer's disease, and Parkinson's disease. nAChRs also play a significant role in nicotine addiction and other health problems associated with tobacco smoking. 3-[2()-2-Azetidinylmethoxy]pyridine (A-85380) is a highly potent and selective α4β2 nAChR agonist with subnanomolar affinity (4, 5). 6-[F]Fluoro-A-85380 and 2-[F]fluoro-A-85380 have been studied in humans as positron emission tomography (PET) agents for α4β2 nAChR imaging in the brain. A-85380 has also been labeled as 5-[I]iodo-A-85380, which has been developed as a single-photon emission computed tomography agent for the non-invasive study of α4β2 nAChR in the brain. There are some implications that α7 nAChRs may play a role in the pathophysiology of neuropsychiatric disorders (6-8); however, there have been no clinical studies of α7 nAChRs using PET ligands. 4-Bromophenyl-1,4-diazabicyclo(3.2.2) nonane-4-carboxylate (SSR180711) has been shown to be a potent and selective partial agonist for α7 nAChRs with nanomolar affinity (9). [Br]SSR180711 is being developed as a PET agent for the non-invasive study of α7 nAChR in the brain (10).