Chapter 5. Targeting nicotinic acetylcholine receptors: Advances in molecular design and therapies

Abstract

Publisher Summary This chapter discusses advances in molecular design and therapies associated with nicotinic acetylcholine receptors (nAChRs), which are members of the ligand-gated ion-channel neurotransmitter family of receptors. These receptors consist of five individual subunit proteins assembled around a central ion-conducting pore. Advances in molecular biology and selective probe design have resulted in the discovery of nine human subunit genes expressed in the central nervous system (CNS). Naming of subunits has been largely chronological, with the exception that alpha subunits contain vicinal disulphides in their extracellular domain. The nAChR subunits are known to oligomerize into both homopentameric and heteropentameric subtypes, each of which possesses distinct ligand specificity, pharmacological profile and distribution in the nervous system. Evidence suggests that modulation of nAChRs may benefit numerous CNS and peripheral nervous system (PNS) disorders. The nAChR approach is particularly attractive where therapeutic intervention is currently limited. An overview of structure-activity relationships of novel nAChR ligands is presented in the chapter. Clinical applications of nAChR ligands are discussed. Neurological and neuroosychiatric disorder and non-CNS diseases are also elaborated.