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The wide range of pharmacologic effects of nicotine and other nicotinic natural products, such as epibatidine, anabasine, lobeline, and cytisine, together with increasing knowledge of the role and function of nicotinic acetylcholine receptors (nAChRs; nicotinic receptor), has led to great interest in the potential of antagonists, agonists, and partial agonists of nAChRs, as treatments for central nervous system (CNS) disorders. Focused efforts to design selective nAChR ligands as new therapeutic agents have been going on for more than two decades, but to date, few synthetic nAChR ligands have been approved for clinical use – nAChR antagonists such as mecamylamine for hypertension in 1950 and the nAChR partial agonist varenicline for smoking cessation in 2006. Evidence is accumulating for the involvement of nAChRs in several CNS disorders in addition to nicotine dependence, including alcoholism, depression, schizophrenia, pain, attention-deficit/hyperactivi...
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References
Albuquerque EX, Pereira EF, Alkondon M, Rogers SW (2009) Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev 89:73–120
Arneric SP, Holladay M, Williams M (2007) Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem Pharmacol 74:1092–1101
Benowitz NL (2009) Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 49:57–71
Changeux JP, Edelstein SJ (2005) Allosteric mechanisms of signal transduction. Science 308:1424–1428
Cincotta SL, Yorek MS, Moschak TM, Lewis SR, Rodefer JS (2008) Selective nicotinic acetylcholine receptor agonists: potential therapies for neuropsychiatric disorders with cognitive dysfunction. Curr Opin Investig Drugs 9:47–56
Dani JA, Bertrand D (2007) Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol 47:699–729
Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR (2008) Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 165:1040–1047
Hogg RC, Bertrand D (2007) Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors. Biochem Pharmacol 73:459–468
Lape R, Colquhoun D, Sivilotti LG (2008) On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454:722–727
Mukhtasimova N, Lee WY, Wang HL, Sine SM (2009) Detection and trapping of intermediate states priming nicotinic receptor channel opening. Nature 459:451–454
Picciotto MR, Addy NA, Mineur YS, Brunzell DH (2008) It is not “either/or”: activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog Neurobiol 84:329–342
Quik M, O’Leary K, Tanner CM (2008) Nicotine and Parkinson’s disease: implications for therapy. Mov Disord 23:1641–1652
Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE (2007) Rationale, pharmacology and clinical efficacy of partial agonists of α4β2 nACh receptors for smoking cessation. Trends Pharmacol Sci 28:316–325
Rusted JM, Newhouse PA, Levin ED (2000) Nicotinic treatment for degenerative neuropsychiatric disorders such as Alzheimer’s disease and Parkinson’s disease. Behav Brain Res 113:121–129
Shytle RD, Silver AA, Lukas RJ, Newman MB, Sheehan DV, Sanberg PR (2002) Nicotinic acetylcholine receptors as targets for antidepressants. Mol Psychiatry 7:525–535
Wilens TE, Decker MW (2007) Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition. Biochem Pharmacol 74:1212–1223
Yang KC, Jin GZ, Wu J (2009) Mysterious α6-containing nAChRs: function, pharmacology, and pathophysiology. Acta Pharmacol Sin 30:740–751
Acknowledgment and Disclosure
HR and RSH are employees of Pfizer, Inc. DB was supported by the Swiss National Science Foundation. Editorial support was provided by Alexandra Bruce, PhD, of UBC Scientific Solutions, and was funded by Pfizer, Inc.
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Rollema, H., Bertrand, D., Hurst, R.S. (2010). Nicotinic Agonists and Antagonists. In: Stolerman, I.P. (eds) Encyclopedia of Psychopharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68706-1_304
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DOI: https://doi.org/10.1007/978-3-540-68706-1_304
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-68698-9
Online ISBN: 978-3-540-68706-1
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