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Leung K1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Dec 12 [updated 2011 Jan 27].

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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD


Neuronal α4β2 nicotinic cholinergic receptors (nAChRs) are part of a heterogeneous family of ligand-gated ion channels expressed in the central nervous system and in peripheral tissues, where their activation by acetylcholine and nicotine causes a rapid increase in cellular permeability to ions such as Na+ and Ca2+ (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(S)-2-Azetidinylmethoxy]pyridine (A-85380) is a highly potent and selective α4β2 nAChR agonist with subnanomolar affinity (4, 5). 6-[18F]Fluoro-A-85380 and 2-[18F]fluoro-A-85380 have been studied in humans as positron emission tomography (PET) agents for α4β2 nAChR imaging in the brain for studying neuropsychiatric disorders. A-85380 has also been labeled as 5-[123I]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. On the other hand, there are some implications that homomeric α7 nAChRs play a role in the pathophysiology of neuropsychiatric disorders (6-8). α7 nAChRs are highly expressed in the cerebral cortex, hippocampus, and subcortical limbic regions, which are involved in learning, memory, and information processing (9-11). 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 (12). 4-[11C]Methylphenyl-1,4-diazabicyclo[3.2.2]nonane-4-carboxylate ([11C]CHIBA-1001) has been developed as a PET agent for the non-invasive study of α7 nAChR in the brain (13). In this chapter, another α7 nAChR agonist, 4-[5-(4-[18F]fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane ([18F]NS10743) (14), is being evaluated for use as a PET imaging agent.

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