Nicotinic receptors as targets for therapeutic discovery.

Nicotinic acetylcholine receptors (nAChRs) represent a class of therapeutic targets with the potential to impact numerous diseases and disorders where significant unmet medical needs remain. The latter include cognitive and neurodegenerative diseases; psychotic disorders, such as schizophrenia; acute nociceptive, neuropathic and inflammatory pain; affective disorders, such as depression and inflammation, where nAChR subtypes modulate key cellular pathways involved in anti-inflammatory processes as well as cell survival. Our increased understanding of the heterogeneity of nAChR targets is defining the relationship of biologic effects to specific receptor subtypes, which in turn, will allow further refinement of desired therapeutic activities. Both preclinical and clinical evidence support the notion that novel compounds targeting specific nAChR subtypes will offer increased potency and efficacy, longer lasting effects, fewer side effects and a more rapid onset of action and less dependence, compared with existing therapies. Clinical proof-of-concept is rapidly emerging and will solidify the position of this new therapeutic approach.