[Nicotine acetylcholine receptors and neuropsychiatric disorders]

This review will be attempt to describe the current knowledge on the neuronal nicotinic acetylcholine receptors (nAChRs) and their involvement in the pathogenesis of a number of neuropsychiatric disorders and the properties of recently synthesized subtype-selective nAChRs. The potential brain therapeutic targets for nAChRs are reviewed.

The nAChRs belong to a family of ligand-gated channels which are widely distributed in brain. Multiple subtypes of these receptors exist, each with diverse structures, individual pharmacological and functional properties. In contrast to the muscular nAChRs, the physiological functions of nAChRs are not well defined to date. In addition, the majority of evidence defining potential therapeutic targets involving nAChRs has resulted from studies on the effects of nicotine in a variety of preclinical and, to a lesser extent, clinical models. The preclinical research continues to focus on nicotine and a number of novel nAChRs agonists have been synthesized in the last few years that may have therapeutic potential in a number of neurological and psychiatric conditions.

The structure of nAChRs and the considerable molecular diversity in subunits offers the possibility of a large number of nAChRs subtypes, which, based on pharmacological precedent, may serve a variety of discrete functions within the brain and thus represent novel targets for therapeutic agents. A promising trend for therapy is the synthesis of new agonists with high nAChRs subtype selectivity, which do not exhibit nicotine's side effects and do show clear beneficial actions in the neuropsychiatric disorders.