Decker_2008_Expert.Opin.Drug.Discov_3_1027

Background: Nicotine has a variety of effects in humans and in experimental animals that are suggestive of therapeutic potential. However, nicotine has a variety of adverse effects that preclude its development as a therapeutic agent, with the exception of its short-term use as a smoking cessation aide. Objective: In this paper, we describe the clinical evidence supporting the potential of new nicotinic acetylcholine receptor (nAChR) agonists for the treatment of CNS conditions and review discovery strategies for targeting neuronal nAChRs as well as some of the opportunities and challenges still ahead. Method: The scientific literature and company websites are used for this literature review. Conclusion: Advances in the understanding of nAChRs during the past two decades have revealed evidence of considerable subtype diversity and hence the possibility of targeted nAChR ligands as improved therapeutics. Several new nAChR agonists have advanced to Phase II clinical trials and have produced signals of efficacy in Alzheimer's disease, attention deficit hyperactivity disorder, cognitive deficits of schizophrenia and pain. In addition, the neuronal nAChR partial agonist varenicline recently received regulatory approval for use in smoking cessation.