Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

General Review Article

NAChR α4β2 Subtype and their Relation with Nicotine Addiction, Cognition, Depression and Hyperactivity Disorder

Author(s): Manuela M. Laikowski, Fávero Reisdorfer and Sidnei Moura*

Volume 26, Issue 20, 2019

Page: [3792 - 3811] Pages: 20

DOI: 10.2174/0929867325666180410105135

Price: $65


Background: Neuronal α4β2 nAChRs are receptors involved in the role of neurotransmitters regulation and release, and this ionic channel participates in biological process of memory, learning and attention. This work aims to review the structure and functioning of the α4β2 nAChR emphasizing its role in the treatment of associated diseases like nicotine addiction and underlying pathologies such as cognition, depression and attention-deficit hyperactivity disorder.

Methods: The authors realized extensive bibliographic research using the descriptors “Nicotine Receptor α4β2” and “cognition”, “depression”, “attention-deficit hyperactivity disorder”, besides cross-references of the selected articles and after analysis of references in the specific literature.

Results: As results, it was that found 179 relevant articles presenting the main molecules with affinity to nAChR α4β2 related to the cited diseases. The α4β2 nAChR subtype is a remarkable therapeutic target since this is the most abundant receptor in the central nervous system.

Conclusion: In summary, this review presents perspectives on the pharmacology and therapeutic targeting of α4β2 nAChRs for the treatment of cognition and diseases like nicotine dependence, depression and attention-deficit hyperactivity disorder.

Keywords: nAChR, α4β2, nicotine addiction, depression, hyperactivity disorder, cognition.

Dani, J.A.; Bertrand, D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 699-729.
[] [PMID: 17009926]
Iturriaga-Vásquez, P.; Alzate-Morales, J.; Bermudez, I.; Varas, R.; Reyes-Parada, M. Multiple binding sites in the nicotinic acetylcholine receptors: An opportunity for polypharmacolgy. Pharmacol. Res., 2015, 101, 9-17.
[] [PMID: 26318763]
Lindstrom, J. The Structure of nAChRs Neuronal Nicotinic Receptors. Handbook of Experimental Pharmacology; Springer: Verlag, Berlin, 2000.
Gotti, C.; Zoli, M.; Clementi, F. Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol. Sci., 2006, 27(9), 482-491.
[] [PMID: 16876883]
Jensen, A.A.; Frølund, B.; Liljefors, T.; Krogsgaard-Larsen, P. Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations. J. Med. Chem., 2005, 48(15), 4705-4745.
[] [PMID: 16033252]
Hamouda, A.K.; Wang, Z.J.; Stewart, D.S.; Jain, A.D.; Glennon, R.A.; Cohen, J.B. Desformylflustrabromine(dFBr) and [3H]dFBr- Labeled binding sites in a nicotinic acetylcholine receptor. Mol. Pharmacol., 2015, 88(1), 1-11.
[] [PMID: 25870334]
Lange-Asschenfeldt, C.; Schäble, S.; Suvorava, T.; Fahimi, E.G.; Bisha, M.; Stermann, T. Effects of varenicline on alpha4-containing nicotinic acetylcholine receptor expression and cognitive performance in mice. Neuropharmacology, 2016, 107100.
Zambrano, C.A.; Short, C.A.; Salamander, R.M.; Grady, S.R.; Marks, M.J. Density of α4β2* nAChR on the surface of neurons is modulated by chronic antagonist exposure. Pharmacol. Res. Perspect., 2015, 3(2), e00111.
[] [PMID: 25729578]
Morales-Perez, C.L.; Noviello, C.M.; Hibbs, R.E. X-ray structure of the human α4β2 nicotinic receptor. Nature, 2016, 538(7625), 411-415.
[] [PMID: 27698419]
Pontieri, F.E.; Tanda, G.; Orzi, F.; Di Chiara, G. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature, 1996, 382(6588), 255-257.
[] [PMID: 8717040]
Corrigall, W.A.; Coen, K.M.; Adamson, K.L. Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res., 1994, 653(1-2), 278-284.
[] [PMID: 7982062]
Benwell, M.E.; Balfour, D.J.; Anderson, J.M. Evidence that tobacco smoking increases the density of (-)-[3H]nicotine binding sites in human brain. J. Neurochem., 1988, 50(4), 1243-1247.
[] [PMID: 3346676]
Flores, C.M.; Rogers, S.W.; Pabreza, L.A.; Wolfe, B.B.; Kellar, K.J. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol. Pharmacol., 1992, 41(1), 31-37.
[PMID: 1732720]
Rose, J.E.; Behm, F.M.; Westman, E.C.; Coleman, R.E. Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend., 1999, 56(2), 99-107.
[] [PMID: 10482401]
Sabey, K.; Paradiso, K.; Zhang, J.; Steinbach, J.H. Ligand binding and activation of rat nicotinic alpha4beta2 receptors stably expressed in HEK293 cells. Mol. Pharmacol., 1999, 55(1), 58-66.
[] [PMID: 9882698]
Laviolette, S.R.; van der Kooy, D. The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour. Nat. Rev. Neurosci., 2004, 5(1), 55-65.
[] [PMID: 14708004]
Dani, J.A.; Harris, R.A. Nicotine addiction and comorbidity with alcohol abuse and mental illness. Nat. Neurosci., 2005, 8(11), 1465-1470.
[] [PMID: 16251989]
Everitt, B.J.; Robbins, T.W. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci., 2005, 8(11), 1481-1489.
[] [PMID: 16251991]
Marubio, L.M.; Gardier, A.M.; Durier, S.; David, D.; Klink, R. Arroyo- Jimenez, M.M.; McIntosh, J.M.; Rossi, F.; Champtiaux, N.; Zoli, M.; Changeux, J.-P. Effects of nicotine in the dopaminergic system of mice lacking the alpha 4 subunit of neuronal nicotinic acetylcholine receptors. Eur. J. Neurosci., 2003, 17, 1327-1337.
Picciotto, M.R.; Zoli, M.; Rimondini, R.; Léna, C.; Marubio, L.M.; Pich, E.M.; Fuxe, K.; Changeux, J.P. Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature, 1998, 391(6663), 173-177.
[] [PMID: 9428762]
Maskos, U.; Molles, B.E.; Pons, S.; Besson, M.; Guiard, B.P.; Guilloux, J.P.; Evrard, A.; Cazala, P.; Cormier, A.; Mameli-Engvall, M.; Dufour, N.; Cloëz-Tayarani, I.; Bemelmans, A.P.; Mallet, J.; Gardier, A.M.; David, V.; Faure, P.; Granon, S.; Changeux, J.P. Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature, 2005, 436(7047), 103-107.
[] [PMID: 16001069]
Rose, J.E.; Levin, E.D. Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence. Pharmacol. Biochem. Behav., 1992, 41(1), 219-226.
[] [PMID: 1539072]
Cohen, C.; Bergis, O.E.; Galli, F.; Lochead, A.W.; Jegham, S.; Biton, B.; Leonardon, J.; Avenet, P.; Sgard, F.; Besnard, F.; Graham, D.; Coste, A.; Oblin, A.; Curet, O.; Voltz, C.; Gardes, A.; Caille, D.; Perrault, G.; George, P.; Soubrie´, P.; Scatton, B. SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation. J. Pharmacol. Exp. Ther., 2003, 306(1), 407-420.
[] [PMID: 12682217]
Prochaska, J.J.; Das, S.; Benowitz, N.L. Cytisine, the world’s oldest smoking cessation aid. BMJ, 2013, 347, f5198.
[] [PMID: 23974638]
Rollema, H.; Chambers, L.K.; Coe, J.W.; Glowa, J.; Hurst, R.S.; Lebel, L.A.; Lu, Y.; Mansbach, R.S.; Mather, R.J.; Rovetti, C.C.; Sands, S.B.; Schaeffer, E.; Schulz, D.W.; Tingley, F.D., III; Williams, K.E. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology, 2007, 52(3), 985-994.
[] [PMID: 17157884]
Etter, J.F. Cytisine for smoking cessation: a literature review and a meta-analysis. Arch. Intern. Med., 2006, 166(15), 1553-1559.
[] [PMID: 16908787]
West, R.; Zatonski, W.; Cedzynska, M.; Lewandowska, D.; Pazik, J.; Aveyard, P.; Stapleton, J. Placebo-controlled trial of cytisine for smoking cessation. N. Engl. J. Med., 2011, 365(13), 1193-1200.
[] [PMID: 21991893]
Leaviss, J.; Sullivan, W.; Ren, S.; Everson-Hock, E.; Stevenson, M.; Stevens, J.W.; Strong, M.; Cantrell, A. What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation. Health Technol. Assess., 2014, 18(33), 1-120.
[] [PMID: 24831822]
Coe, J.W.; Brooks, P.R.; Wirtz, M.C.; Bashore, C.G.; Bianco, K.E.; Vetelino, M.G.; Arnold, E.P.; Lebel, L.A.; Fox, C.B.; Tingley, F.D., III; Schulz, D.W.; Davis, T.I.; Sands, S.B.; Mansbach, R.S.; Rollema, H.; O’Neill, B.T. 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg. Med. Chem. Lett., 2005, 15(22), 4889-4897.
[] [PMID: 16171993]
Rollema, H.; Coe, J.W.; Chambers, L.K.; Hurst, R.S.; Stahl, S.M.; Williams, K.E. Rationale, pharmacology and clinical efficacy of partial agonists of α4β2 nACh receptors for smoking cessation. Trends Pharmacol. Sci., 2007, 28(7), 316-325.
[] [PMID: 17573127]
Coe, J.W.; Brooks, P.R.; Vetelino, M.G.; Wirtz, M.C.; Arnold, E.P.; Huang, J.; Sands, S.B.; Davis, T.I.; Lebel, L.A.; Fox, C.B.; Shrikhande, A.; Heym, J.H.; Schaeffer, E.; Rollema, H.; Lu, Y.; Mansbach, R.S.; Chambers, L.K.; Rovetti, C.C.; Schulz, D.W.; Tingley, F.D., III; O’Neill, B.T. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J. Med. Chem., 2005, 48(10), 3474-3477.
[] [PMID: 15887955]
Rollema, H.; Chambers, L.K.; Coe, J.W.; Glowa, J.; Hurst, R.S.; Lebel, L.A.; Lu, Y.; Mansbach, R.S.; Mather, R.J.; Rovetti, C.C.; Sands, S.B.; Schaeffer, E.; Schulz, D.W.; Tingley, F.D., III; Williams, K.E. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology, 2007, 52(3), 985-994.
[] [PMID: 17157884]
Mihalak, K.B.; Carroll, F.I.; Luetje, C.W. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol. Pharmacol., 2006, 70(3), 801-805.
[] [PMID: 16766716]
Lummis, S.C.; Thompson, A.J.; Bencherif, M.; Lester, H.A. Varenicline is a potent agonist of the human 5-hydroxytryptamine3 receptor. J. Pharmacol. Exp. Ther., 2011, 339(1), 125-131.
[] [PMID: 21775477]
Reperant, C.; Pons, S.; Dufour, E.; Rollema, H.; Gardier, A.M.; Maskos, U. Effect of the a4b2 on dopamine release in b2 knock-out mice with selective re-expression of the b2 subunit in the ventral tegmental area. Neuropharmacology, 2010, 58, 346-350.
[] [PMID: 19887076]
Mohamed, T.S.; Jayakar, S.S.; Hamouda, A.K. Orthosteric and allosteric ligands of nicotinic acetylcholine receptors for smoking cessation. Front. Mol. Neurosci., 2015, 8, 71.
[] [PMID: 26635524]
Cohen, C.; Bergis, O.E.; Galli, F.; Lochead, A.W.; Jegham, S.; Biton, B.; Leonardon, J.; Avenet, P.; Sgard, F.; Besnard, F.; Graham, D.; Coste, A.; Oblin, A.; Curet, O.; Voltz, C.; Gardes, A.; Caille, D.; Perrault, G.; George, P.; Soubrie, P.; Scatton, B. SSR591813, a novel selective and partial α4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation. J. Pharmacol. Exp. Ther., 2003, 306(1), 407-420.
[] [PMID: 12682217]
Coe, J.W.; Vetelino, M.G.; Bashore, C.G.; Wirtz, M.C.; Brooks, P.R.; Arnold, E.P.; Lebel, L.A.; Fox, C.B.; Sands, S.B.; Davis, T.I.; Schulz, D.W.; Rollema, H.; Tingley, F.D., III; O’Neill, B.T. In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine. Bioorg. Med. Chem. Lett., 2005, 15(12), 2974-2979.
[] [PMID: 15908213]
Rose, J.E.; Behm, F.M.; Westman, E.C.; Coleman, R.E. Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend., 1999, 56(2), 99-107.
[] [PMID: 10482401]
Faessel, H.M.; Gibbs, M.A.; Clark, D.J.; Rohrbacher, K.; Stolar, M.; Burstein, A.H. Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy smokers. J. Clin. Pharmacol., 2006, 46(12), 1439-1448.
[] [PMID: 17101743]
Slemmer, J.E.; Martin, B.R.; Damaj, M.I. Bupropion is a nicotinic antagonist. J. Pharmacol. Exp. Ther., 2000, 295(1), 321-327.
[PMID: 10991997]
Damaj, M.I.; Carroll, F.I.; Eaton, J.B.; Navarro, H.A.; Blough, B.E.; Mirza, S.; Lukas, R.J.; Martin, B.R. Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. Mol. Pharmacol., 2004, 66(3), 675-682.
[] [PMID: 15322260]
Fiore, M.C. Treating Tobacco Use and Dependence: Clinical Practice Guideline; US Department of Health and Human Services, Public Health Service, 2000.
Dwoskin, L.P.; Rauhut, A.S.; King-Pospisil, K.A.; Bardo, M.T. Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Rev., 2006, 12(3-4), 178-207.
[] [PMID: 17227286]
Lerman, C.; LeSage, M.G.; Perkins, K.A.; O’Malley, S.S.; Siegel, S.J.; Benowitz, N.L.; Corrigall, W.A. Translational research in medication development for nicotine dependence. Nat. Rev. Drug Discov., 2007, 6(9), 746-762.
[] [PMID: 17690709]
Igari, M.; Alexander, J.C.; Ji, Y.; Qi, X.; Papke, R.L.; Bruijnzeel, A.W. Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats. Neuropsychopharmacology, 2014, 39(2), 455-465.
[] [PMID: 23966067]
Williams, D.K.; Wang, J.; Papke, R.L. Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations. Biochem. Pharmacol., 2011, 82(8), 915-930.
[] [PMID: 21575610]
Taly, A.; Corringer, P.J.; Guedin, D.; Lestage, P.; Changeux, J.P. Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat. Rev. Drug Discov., 2009, 8(9), 733-750.
[] [PMID: 19721446]
Uteshev, V.V. The therapeutic promise of positive allosteric modulation of nicotinic receptors. Eur. J. Pharmacol., 2014, 727, 181-185.
[] [PMID: 24530419]
Liu, X. Positive allosteric modulation of α4β2 nicotinic acetylcholine receptors as a new approach to smoking reduction: evidence from a rat model of nicotine self-administration. Psychopharmacology (Berl.), 2013, 230(2), 203-213.
[] [PMID: 23712602]
Maelicke, A.; Samochocki, M.; Jostock, R.; Fehrenbacher, A.; Ludwig, J.; Albuquerque, E.X.; Zerlin, M. Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer’s disease. Biol. Psychiatry, 2001, 49(3), 279-288.
[] [PMID: 11230879]
Sala, F.; Mulet, J.; Reddy, K.P.; Bernal, J.A.; Wikman, P.; Valor, L.M.; Peters, L.; König, G.M.; Criado, M.; Sala, S. Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite. Neurosci. Lett., 2005, 373(2), 144-149.
[] [PMID: 15567570]
Kim, J.S.; Padnya, A.; Weltzin, M.; Edmonds, B.W.; Schulte, M.K.; Glennon, R.A. Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator. Bioorg. Med. Chem. Lett., 2007, 17(17), 4855-4860.
[] [PMID: 17604168]
Pandya, A.; Yakel, J.L. Allosteric modulator Desformylflustrabromine relieves the inhibition of α2β2 and α4β2 nicotinic acetylcholine receptors by β-amyloid(1-42) peptide. J. Mol. Neurosci., 2011, 45(1), 42-47.
[] [PMID: 21424792]
Weltzin, M.M.; Schulte, M.K. Desformylflustrabromine Modulates α4β2 Neuronal Nicotinic Acetylcholine Receptor High- and Low-Sensitivity Isoforms at Allosteric Clefts Containing the β2 Subunit. J. Pharmacol. Exp. Ther., 2015, 354(2), 184-194.
[] [PMID: 26025967]
Albrecht, B.K.; Berry, V.; Boezio, A.A.; Cao, L.; Clarkin, K.; Guo, W.; Harmange, J.C.; Hierl, M.; Huang, L.; Janosky, B.; Knop, J.; Malmberg, A.; McDermott, J.S.; Nguyen, H.Q.; Springer, S.K.; Waldon, D.; Woodin, K.; McDonough, S.I. Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant alpha4beta2 nicotinic acetylcholine receptor potentiators. Bioorg. Med. Chem. Lett., 2008, 18(19), 5209-5212.
[] [PMID: 18789861]
Springer, S.K.; Woodin, K.S.; Berry, V.; Boezio, A.A.; Cao, L.; Clarkin, K.; Harmange, J.C.; Hierl, M.; Knop, J.; Malmberg, A.B.; McDermott, J.S.; Nguyen, H.Q.; Waldon, D.; Albrecht, B.K.; McDonough, S.I. Synthesis and activity of substituted carbamates as potentiators of the alpha4beta2 nicotinic acetylcholine receptor. Bioorg. Med. Chem. Lett., 2008, 18(20), 5643-5647.
[] [PMID: 18805006]
Timmermann, D.B.; Sandager-Nielsen, K.; Dyhring, T.; Smith, M.; Jacobsen, A.M.; Nielsen, E.Ø.; Grunnet, M.; Christensen, J.K.; Peters, D.; Kohlhaas, K.; Olsen, G.M.; Ahring, P.K. Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors. Br. J. Pharmacol., 2012, 167(1), 164-182.
[] [PMID: 22506660]
Olsen, J.A.; Ahring, P.K.; Kastrup, J.S.; Gajhede, M.; Balle, T. Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors. J. Biol. Chem., 2014, 289(36), 24911-24921.
[] [PMID: 24982426]
Maurer, J.J.; Sandager-Nielsen, K.; Schmidt, H.D. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283. Psychopharmacology (Berl.), 2017, 234(3), 475-484.
[] [PMID: 27844094]
Janowsky, D.S.; el-Yousef, M.K.; Davis, J.M.; Sekerke, H.J. A cholinergic-adrenergic hypothesis of mania and depression. Lancet, 1972, 2(7778), 632-635.
[] [PMID: 4116781]
Philip, N.S.; Carpenter, L.L.; Tyrka, A.R.; Price, L.H. Nicotinic acetylcholine receptors and depression: a review of the preclinical and clinical literature. Psychopharmacology (Berl.), 2010, 212(1), 1-12.
[] [PMID: 20614106]
Gotti, C.; Riganti, L.; Vailati, S.; Clementi, F. Brain neuronal nicotinic receptors as new targets for drug discovery. Curr. Pharm. Des., 2006, 12(4), 407-428.
[] [PMID: 16472136]
Albuquerque, E.X.; Pereira, E.F.; Alkondon, M.; Rogers, S.W. Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol. Rev., 2009, 89(1), 73-120.
[] [PMID: 19126755]
Yu, L.F.; Zhang, H.K.; Caldarone, B.J.; Eaton, J.B.; Lukas, R.J.; Kozikowski, A.P. Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors. J. Med. Chem., 2014, 57(20), 8204-8223.
[] [PMID: 24901260]
Arneric, S.P.; Holladay, M.; Williams, M. Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem. Pharmacol., 2007, 74(8), 1092-1101.
[] [PMID: 17662959]
George, T.P.; Sacco, K.A.; Vessicchio, J.C.; Weinberger, A.H.; Shytle, R.D. Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. J. Clin. Psychopharmacol., 2008, 28(3), 340-344.
[] [PMID: 18480694]
Shytle, R.D.; Silver, A.A.; Lukas, R.J.; Newman, M.B.; Sheehan, D.V.; Sanberg, P.R. Nicotinic acetylcholine receptors as targets for antidepressants. Mol. Psychiatry, 2002, 7(6), 525-535.
[] [PMID: 12140772]
Philip, N.S.; Carpenter, L.L.; Tyrka, A.R.; Whiteley, L.B.; Price, L.H. Varenicline augmentation in depressed smokers: an 8-week, open-label study. J. Clin. Psychiatry, 2009, 70(7), 1026-1031.
[] [PMID: 19323966]
Furey, M.L.; Drevets, W.C. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch. Gen. Psychiatry, 2006, 63(10), 1121-1129.
[] [PMID: 17015814]
Drevets, W.C.; Furey, M.L. Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol. Psychiatry, 2010, 67(5), 432-438.
[] [PMID: 20074703]
Arias, H.R.; Rosenberg, A.; Targowska-Duda, K.M.; Feuerbach, D.; Jozwiak, K.; Moaddel, R.; Wainer, I.W. Tricyclic antidepressants and mecamylamine bind to different sites in the human alpha4beta2 nicotinic receptor ion channel. Int. J. Biochem. Cell Biol., 2010, 42(6), 1007-1018.
[] [PMID: 20223294]
Hennings, E.C.; Kiss, J.P.; Vizi, E.S. Nicotinic acetylcholine receptor antagonist effect of fluoxetine in rat hippocampal slices. Brain Res., 1997, 759(2), 292-294.
[] [PMID: 9221950]
Fryer, J.D.; Lukas, R.J. Antidepressants noncompetitively inhibit nicotinic acetylcholine receptor function. J. Neurochem., 1999, 72(3), 1117-1124.
[] [PMID: 10037483]
López-Valdés, H.E.; García-Colunga, J. Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamine uptake. Mol. Psychiatry, 2001, 6(5), 511-519.
[] [PMID: 11526465]
Weber, M.L.; Hofland, C.M.; Shaffer, C.L.; Flik, G.; Cremers, T.; Hurst, R.S.; Rollema, H. Therapeutic doses of antidepressants are projected not to inhibit human α4β2 nicotinic acetylcholine receptors. Neuropharmacology, 2013, 72, 88-95.
[] [PMID: 23639435]
Popik, P.; Kozela, E.; Krawczyk, M. Nicotine and nicotinic receptor antagonists potentiate the antidepressant-like effects of imipramine and citalopram. Br. J. Pharmacol., 2003, 139(6), 1196-1202.
[] [PMID: 12871839]
Andreasen, J.T.; Nielsen, E.O.; Christensen, J.K.; Olsen, G.M.; Peters, D.; Mirza, N.R.; Redrobe, J.P. Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test. J. Psychopharmacol. (Oxford), 2011, 25(10), 1347-1356.
[] [PMID: 20360159]
Caldarone, B.J.; Harrist, A.; Cleary, M.A.; Beech, R.D.; King, S.L.; Picciotto, M.R. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biol. Psychiatry, 2004, 56(9), 657-664.
[] [PMID: 15522249]
Rabenstein, R.L.; Caldarone, B.J.; Picciotto, M.R. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice. Psychopharmacology (Berl.), 2006, 189(3), 395-401.
[] [PMID: 17016705]
Caldarone, B.J.; Wang, D.; Paterson, N.E.; Manzano, M.; Fedolak, A.; Cavino, K.; Kwan, M.; Hanania, T.; Chellappan, S.K.; Kozikowski, A.P.; Olivier, B.; Picciotto, M.R.; Ghavami, A. Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380. Psychopharmacology (Berl.), 2011, 217(2), 199-210.
[] [PMID: 21487659]
Lippiello, P.M.; Beaver, J.S.; Gatto, G.J.; James, J.W.; Jordan, K.G.; Traina, V.M.; Xie, J.; Bencherif, M. TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity. CNS Neurosci. Ther., 2008, 14(4), 266-277.
[] [PMID: 19040552]
Targacept’s TC-5214 achieves all primary and secondary outcome measures in Phase 2b trial as augmentation treatment for major depressive disorder. Targacept, Inc. Available at: [Accessed date:July15, 2009]
A study to assess the efficacy and safety of TC-5214 as an adjunct therapy in patients with major depressive disorder (MDD). Available at: 157078?term=TC5214&rank=17 [Accessed date: December 29, 2011
A study to assess the efficacy and safety of TC-5214 as an adjunct therapy in patients with major depressive disorder. Available at:[Accessed date: November 19, 2012
A study to assess the efficacy and safety of TC-5214 as an adjunct therapy in patients with major depressive disorder. Available at: [Accessed date: November 19, 2012]
Vieta, E.; Thase, M.E.; Naber, D.; D’Souza, B.; Rancans, E.; Lepola, U.; Olausson, B.; Szamosi, J.; Wilson, E.; Hosford, D.; Dunbar, G.; Tummala, R.; Eriksson, H. Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant. Eur. Neuropsychopharmacol., 2014, 24(4), 564-574.
[] [PMID: 24507016]
Ferry, L.H.; Burchette, R.J. Evaluation of bupropion versus placebo for treatment of nicotine dependence 147th Annual Meeting of the American Psychiatric Association, Philadelphia, PA1994, pp. 199-200.
Damaj, M.I.; Carroll, F.I.; Eaton, J.B.; Navarro, H.A.; Blough, B.E.; Mirza, S.; Lukas, R.J.; Martin, B.R. Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. Mol. Pharmacol., 2004, 66(3), 675-682.
[] [PMID: 15322260]
Fryer, J.D.; Lukas, R.J. Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. J. Pharmacol. Exp. Ther., 1999, 288(1), 88-92.
[PMID: 9862757]
Harvey, S.C.; Maddox, F.N.; Luetje, C.W. Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal nicotinic receptor alpha subunits. J. Neurochem., 1996, 67(5), 1953-1959.
[] [PMID: 8863500]
Daviss, W.B.; Perel, J.M.; Brent, D.A.; Axelson, D.A.; Rudolph, G.R.; Gilchrist, R.; Nuss, S.; Birmaher, B. Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study. Ther. Drug Monit., 2006, 28(2), 190-198.
[] [PMID: 16628130]
Andreasen, J.T.; Olsen, G.M.; Wiborg, O.; Redrobe, J.P. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. J. Psychopharmacol. (Oxford), 2009, 23(7), 797-804.
[] [PMID: 18583432]
Scharfenberg, G.; Benndorf, S.; Kempe, G. [Cytisine (Tabex) as a pharmaceutical aid in stopping smoking Dtsch. Gesundheitsw., 1971, 26(10), 463-465. [Cytisine (Tabex) as a pharmaceutical aid in stopping smoking.
[PMID: 4930772]
Mineur, Y.S.; Eibl, C.; Young, G.; Kochevar, C.; Papke, R.L.; Gündisch, D.; Picciotto, M.R. Cytisine-based nicotinic partial agonists as novel antidepressant compounds. J. Pharmacol. Exp. Ther., 2009, 329(1), 377-386.
[] [PMID: 19164465]
Mineur, Y.S.; Somenzi, O.; Picciotto, M.R. Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice. Neuropharmacology, 2007, 52(5), 1256-1262.
[] [PMID: 17320916]
Coe, J.W.; Vetelino, M.G.; Bashore, C.G.; Wirtz, M.C.; Brooks, P.R.; Arnold, E.P.; Lebel, L.A.; Fox, C.B.; Sands, S.B.; Davis, T.I.; Schulz, D.W.; Rollema, H.; Tingley, F.D., III; O’Neill, B.T. In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine. Bioorg. Med. Chem. Lett., 2005, 15(12), 2974-2979.
[] [PMID: 15908213]
Etter, J.F. Cytisine for smoking cessation: a literature review and a meta-analysis. Arch. Intern. Med., 2006, 166(15), 1553-1559.
[] [PMID: 16908787]
Reavill, C.; Walther, B.; Stolerman, I.P.; Testa, B. Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline. Neuropharmacology, 1990, 29(7), 619-624.
[] [PMID: 2385332]
Barlow, R.B.; McLeod, L.J. Some studies on cytisine and its methylated derivatives. Br. J. Pharmacol., 1969, 35(1), 161-174.
[] [PMID: 4387392]
Rollema, H.; Shrikhande, A.; Ward, K.M.; Tingley, F.D., III; Coe, J.W.; O’Neill, B.T.; Tseng, E.; Wang, E.Q.; Mather, R.J.; Hurst, R.S.; Williams, K.E.; de Vries, M.; Cremers, T.; Bertrand, S.; Bertrand, D. Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence. Br. J. Pharmacol., 2010, 160(2), 334-345.
[] [PMID: 20331614]
Rollema, H.; Guanowsky, V.; Mineur, Y.S.; Shrikhande, A.; Coe, J.W.; Seymour, P.A.; Picciotto, M.R. Varenicline has antidepressant-like activity in the forced swim test and augments sertraline’s effect. Eur. J. Pharmacol., 2009, 605(1-3), 114-116.
[] [PMID: 19168054]
Patterson, F.; Jepson, C.; Strasser, A.A.; Loughead, J.; Perkins, K.A.; Gur, R.C.; Frey, J.M.; Siegel, S.; Lerman, C. Varenicline improves mood and cognition during smoking abstinence. Biol. Psychiatry, 2009, 65(2), 144-149.
[] [PMID: 18842256]
Turner, J.R.; Castellano, L.M.; Blendy, J.A. Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behavior. J. Pharmacol. Exp. Ther., 2010, 334(2), 665-672.
[] [PMID: 20435920]
Rezvani, A.H.; Timofeeva, O.; Sexton, H.G.; DeCuir, D.; Xiao, Y.; Gordon, C.J.; Kellar, K.J.; Levin, E.D. Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats. Eur. J. Pharmacol., 2012, 682(1-3), 110-117.
[] [PMID: 22387853]
Levin, E.D.; Sexton, H.G.; Gordon, K.; Gordon, C.J.; Xiao, Y.; Kellar, K.J.; Yenugonda, V.M.; Liu, Y.; White, M.P.; Paige, M.; Brown, M.L.; Rezvani, A.H. Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice. Eur. J. Pharmacol., 2013, 718(1-3), 167-172.
[] [PMID: 24036108]
Rezvani, A.H.; Cauley, M.; Xiao, Y.; Kellar, K.J.; Levin, E.D. Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats. Psychopharmacology (Berl.), 2013, 226(1), 35-43.
[] [PMID: 23100170]
Cucchiaro, G.; Xiao, Y.; Gonzalez-Sulser, A.; Kellar, K.J. Analgesic effects of Sazetidine-A, a new nicotinic cholinergic drug. Anesthesiology, 2008, 109(3), 512-519.
[] [PMID: 18719450]
Rezvani, A.H.; Cauley, M.; Sexton, H.; Xiao, Y.; Brown, M.L.; Paige, M.A.; McDowell, B.E.; Kellar, K.J.; Levin, E.D. Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats. Psychopharmacology (Berl.), 2011, 215(4), 621-630.
[] [PMID: 21274704]
Turner, J.R.; Wilkinson, D.S.; Poole, R.L.; Gould, T.J.; Carlson, G.C.; Blendy, J.A. Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal. Neuropsychopharmacology, 2013, 38(10), 2035-2047.
[] [PMID: 23624742]
Hussmann, G.P.; DeDominicis, K.E.; Turner, J.R.; Yasuda, R.P.; Klehm, J.; Forcelli, P.A.; Xiao, Y.; Richardson, J.R.; Sahibzada, N.; Wolfe, B.B.; Lindstrom, J.; Blendy, J.A.; Kellar, K.J. Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J. Neurochem., 2014, 129(4), 721-731.
[] [PMID: 24422997]
Johnson, J.E.; Slade, S.; Wells, C.; Petro, A.; Sexton, H.; Rezvani, A.H.; Brown, M.L.; Paige, M.A.; McDowell, B.E.; Xiao, Y.; Kellar, K.J.; Levin, E.D. Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats. Psychopharmacology (Berl.), 2012, 222(2), 269-276.
[] [PMID: 22297831]
Levin, E.D.; Rezvani, A.H.; Xiao, Y.; Slade, S.; Cauley, M.; Wells, C.; Hampton, D.; Petro, A.; Rose, J.E.; Brown, M.L.; Paige, M.A.; McDowell, B.E.; Kellar, K.J. Sazetidine-A, a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist, reduces nicotine self-administration in rats. J. Pharmacol. Exp. Ther., 2010, 332(3), 933-939.
[] [PMID: 20007754]
Rezvani, A.H.; Slade, S.; Wells, C.; Petro, A.; Lumeng, L.; Li, T.K.; Xiao, Y.; Brown, M.L.; Paige, M.A.; McDowell, B.E.; Rose, J.E.; Kellar, K.J.; Levin, E.D. Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats. Psychopharmacology (Berl.), 2010, 211(2), 161-174.
[] [PMID: 20535453]
Liu, J.; Yu, L.F.; Eaton, J.B.; Caldarone, B.; Cavino, K.; Ruiz, C.; Terry, M.; Fedolak, A.; Wang, D.; Ghavami, A.; Lowe, D.A.; Brunner, D.; Lukas, R.J.; Kozikowski, A.P. Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression. J. Med. Chem., 2011, 54(20), 7280-7288.
[] [PMID: 21905669]
Yuan, Y.; Yu, L.F.; Qiu, X.; Kozikowski, A.P.; van Breemen, R.B. Pharmacokinetics and brain penetration of LF-3-88, (2-[5-[5-(2(S)-azetidinylmethoxyl)-3-pyridyl]-3-isoxazolyl]ethanol), a selective α4β2-nAChR partial agonist and promising antidepressant. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 912, 38-42.
[] [PMID: 23246847]
Rahman, S. Targeting brain nicotinic acetylcholine receptors to treat major depression and co-morbid alcohol or nicotine addiction. CNS Neurol. Disord. Drug Targets, 2015, 14(5), 647-653.
[] [PMID: 25921743]
Rahman, S.; Engleman, E.A.; Bell, R.L. Recent advances in nicotinic receptor signaling in alcohol abuse and alcoholism. Prog. Mol. Biol. Transl. Sci., 2016, 137, 183-201.
[] [PMID: 26810002]
Kessler, R.C.; Nelson, C.B.; McGonagle, K.A.; Edlund, M.J.; Frank, R.G.; Leaf, P.J. The epidemiology of co-occurring addictive and mental disorders: implications for prevention and service utilization. Am. J. Orthopsychiatry, 1996, 66(1), 17-31.
[] [PMID: 8720638]
Schuckit, M.A.; Tipp, J.E.; Bergman, M.; Reich, W.; Hesselbrock, V.M.; Smith, T.L. Comparison of induced and independent major depressive disorders in 2,945 alcoholics. Am. J. Psychiatry, 1997, 154(7), 948-957.
[] [PMID: 9210745]
Bell, R.L.; Eiler, B.J., II; Cook, J.B.; Rahman, S. Nicotinic receptor ligands reduce ethanol intake by high alcohol-drinking HAD-2 rats. Alcohol, 2009, 43(8), 581-592.
[] [PMID: 20004336]
Sajja, R.K.; Dwivedi, C.; Rahman, S. Nicotinic ligands modulate ethanol-induced dopamine function in mice. Pharmacology, 2010, 86(3), 168-173.
[] [PMID: 20714207]
Sajja, R.K.; Rahman, S. Lobeline and cytisine reduce voluntary ethanol drinking behavior in male C57BL/6J mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35, 257e264..
Sajja, R.K.; Rahman, S. Neuronal nicotinic receptor ligands modulate chronic nicotine-induced ethanol consumption in C57BL/6J mice. Pharmacol. Biochem. Behav., 2012, 102(1), 36-43.
[] [PMID: 22741175]
Roni, M.A.; Rahman, S. Neuronal nicotinic receptor antagonist reduces anxiety-like behavior in mice. Neurosci. Lett., 2011, 504(3), 237-241.
[] [PMID: 21964392]
Roni, M.A.; Rahman, S. Antidepressant-like effects of lobeline in mice: behavioral, neurochemical, and neuroendocrine evidence. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 41, 44-51.
[] [PMID: 23200829]
Roni, M.A.; Rahman, S. Effects of lobeline and reboxetine, fluoxetine, or bupropion combination on depression-like behaviors in mice. Pharmacol. Biochem. Behav.,, 2015, 139(Pt A), 1-6.
Roni, M.A.; Rahman, S. The effects of lobeline on depression-like behavior and hippocampal cell proliferation following chronic stress in mice. Neurosci. Lett., 2015, 584, 7-11.
[] [PMID: 25451721]
Roni, M.A.; Rahman, S. The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice. Psychopharmacology (Berl.), 2014, 231(15), 2989-2998.
[] [PMID: 24682499]
Roni, M.A.; Rahman, S. Lobeline attenuates ethanol abstinence-induced depression-like behavior in mice. Alcohol, 2017, 61(61), 63-70.
[] [PMID: 28554528]
Braida, D.; Ponzoni, L.; Martucci, R.; Sparatore, F.; Gotti, C.; Sala, M. Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish. Psychopharmacology (Berl.), 2014, 231(9), 1975-1985.
[] [PMID: 24311357]
Kenney, J.W.; Gould, T.J. Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol. Neurobiol., 2008, 38(1), 101-121.
[] [PMID: 18690555]
Placzek, A.N.; Zhang, T.A.; Dani, J.A. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus. Acta Pharmacol. Sin., 2009, 30(6), 752-760.
[] [PMID: 19434057]
Heishman, S.J.; Kleykamp, B.A.; Singleton, E.G. Metaanalysis of the acute effects of nicotine and smoking on human performance. Psychopharmacol., (Berlin), 2010, 210, 453-469.
Hahn, B.; Sharples, C.G.V.; Wonnacott, S.; Shoaib, M.; Stolerman, I.P. Attentional effects of nicotinic agonists in rats. Neuropharmacology, 2003, 44(8), 1054-1067.
[] [PMID: 12763099]
Bitner, R.S.; Bunnelle, W.H.; Anderson, D.J.; Briggs, C.A.; Buccafusco, J.; Curzon, P.; Decker, M.W.; Frost, J.M.; Gronlien, J.H.; Gubbins, E.; Li, J.; Malysz, J.; Markosyan, S.; Marsh, K.; Meyer, M.D.; Nikkel, A.L.; Radek, R.J.; Robb, H.M.; Timmermann, D.; Sullivan, J.P.; Gopalakrishnan, M. Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J. Neurosci., 2007, 27(39), 10578-10587.
[] [PMID: 17898229]
Howe, W.M.; Ji, J.; Parikh, V.; Williams, S.; Mocaër, E.; Trocmé-Thibierge, C.; Sarter, M. Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms. Neuropsychopharmacology, 2010, 35(6), 1391-1401.
[] [PMID: 20147893]
Castner, S.A.; Smagin, G.N.; Piser, T.M.; Wang, Y.; Smith, J.S.; Christian, E.P.; Mrzljak, L.; Williams, G.V. Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors. Biol. Psychiatry, 2011, 69(1), 12-18.
[] [PMID: 20965497]
Lendvai, B.; Kassai, F.; Szájli, A.; Némethy, Z. α7 nicotinic acetylcholine receptors and their role in cognition. Brain Res. Bull., 2013, 93, 86-96.
[] [PMID: 23178154]
Rollema, H.; Hajós, M.; Seymour, P.A.; Kozak, R.; Majchrzak, M.J.; Guanowsky, V.; Horner, W.E.; Chapin, D.S.; Hoffmann, W.E.; Johnson, D.E.; McLean, S.; Freeman, J.; Williams, K.E. Preclinical pharmacology of the α4β2 nAChR partial agonist varenicline related to effects on reward, mood and cognition. Biochem. Pharmacol., 2009, 78(7), 813-824.
[] [PMID: 19501054]
Davis, J.A.; Gould, T.J. Hippocampal nAChRs mediate nicotine withdrawal-related learning deficits. Eur. Neuropsychopharmacol., 2009, 19(8), 551-561.
[] [PMID: 19278836]
Kendziorra, K.; Meyer, P.; Wolf, H.; Barthel, H.; Hesse, S.; Seese, A.; Sorger, D.; Patt, M.; Gertz, J.; Sabri, O. Cerebral nicotinic acetylcholine receptors (nAChRs) in patients with Alzheimer’s disease (AD) assessed with 2-F18-A85380 (2-FA) PET-correlations to dementia severity. J. Nucl. Med., 2006, 47(Suppl. 1), 8.
Felix, R.; Levin, E.D. Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats. Neuroscience, 1997, 81(4), 1009-1017.
[] [PMID: 9330363]
Hidaka, N.; Suemaru, K.; Kato, Y.; Araki, H. Involvement of α4β2 nicotinic acetylcholine receptors in working memory impairment induced by repeated electroconvulsive seizures in rats. Epilepsy Res., 2013, 104(1-2), 181-185.
[] [PMID: 23219030]
Picciotto, M.R.; Lewis, A.S.; van Schalkwyk, G.I.; Mineur, Y.S. Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology, 2015, 96(Pt B), 235-243.
[] [PMID: 25582289]
Diagnostic and Statistical Manual of Mental Disorders, (5th edition. ), , 2013. (DSM-5).
Döpfner, M.; Hautmann, C.; Görtz-Dorten, A.; Klasen, F.; Ravens-Sieberer, U. Long-term course of ADHD symptoms from childhood to early adulthood in a community sample. Eur. Child Adolesc. Psychiatry, 2015, 24(6), 665-673.
[] [PMID: 25395380]
Faraone, S.V.; Perlis, R.H.; Doyle, A.E.; Smoller, J.W.; Goralnick, J.J.; Holmgren, M.A.; Sklar, P. Molecular genetics of attention-deficit/hyperactivity disorder. Biol. Psychiatry, 2005, 57(11), 1313-1323.
[] [PMID: 15950004]
Kessler, R.C.; Adler, L.A.; Barkley, R.; Biederman, J.; Conners, C.K.; Greenhill, L.L.; Spencer, T. The prevalence and correlates of adult ADHD. ADHD in adults: characterization, diagnosis, and treatment,, 2011, 9-17.
Huang, X. Xu, Y.; Li, Q.; Liu, P.; Yang, Y.; Zhang, F.;... & Guo, L. Nicotinic acetylcholine receptor α4 subunit gene variation associated with attention deficit hyperactivity disorder. Tsinghua Sci. Technol., 2009, 14(4), 534-540.
Watterson, E.; Spitzer, A.; Watterson, L.R.; Brackney, R.J.; Zavala, A.R.; Olive, M.F.; Sanabria, F. Nicotine-induced behavioral sensitization in an adult rat model of attention deficit/hyperactivity disorder (ADHD). Behav. Brain Res., 2016, 312, 333-340.
[] [PMID: 27363925]
Pomerleau, O.F.; Downey, K.K.; Stelson, F.W.; Pomerleau, C.S. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J. Subst. Abuse, 1995, 7(3), 373-378.
[] [PMID: 8749796]
Milberger, S.; Biederman, J.; Faraone, S.V.; Chen, L.; Jones, J. ADHD is associated with early initiation of cigarette smoking in children and adolescents. J. Am. Acad. Child Adolesc. Psychiatry, 1997, 36(1), 37-44.
[] [PMID: 9000779]
Lambert, N.M.; Hartsough, C.S. Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J. Learn. Disabil., 1998, 31(6), 533-544.
[] [PMID: 9813951]
Lerman, C.; Audrain, J.; Tercyak, K.; Hawk, L.W., Jr; Bush, A.; Crystal-Mansour, S.; Rose, C.; Niaura, R.; Epstein, L.H. Attention-Deficit Hyperactivity Disorder (ADHD) symptoms and smoking patterns among participants in a smoking-cessation program. Nicotine Tob. Res., 2001, 3(4), 353-359.
[] [PMID: 11694203]
Wilens, T.E.; Vitulano, M.; Upadhyaya, H.; Adamson, J.; Sawtelle, R.; Utzinger, L.; Biederman, J. Cigarette smoking associated with attention deficit hyperactivity disorder. J. Pediatr., 2008, 153(3), 414-419.
[] [PMID: 18534619]
Kollins, S.H.; McClernon, F.J.; Fuemmeler, B.F. Association between smoking and attention-deficit/hyperactivity disorder symptoms in a population-based sample of young adults. Arch. Gen. Psychiatry, 2005, 62(10), 1142-1147.
[] [PMID: 16203959]
Potter, A.S.; Newhouse, P.A.; Bucci, D.J. Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder? Behav. Brain Res., 2006, 175(2), 201-211.
[] [PMID: 17081628]
Levin, E.D.; Rezvani, A.H. Nicotinic treatment for cognitive dysfunction. Curr. Drug Targets CNS Neurol. Disord., 2002, 1(4), 423-431.
[] [PMID: 12769614]
Newhouse, P.A.; Potter, A.; Singh, A. Effects of nicotinic stimulation on cognitive performance. Curr. Opin. Pharmacol., 2004, 4(1), 36-46.
[] [PMID: 15018837]
Sacco, K.A.; Bannon, K.L.; George, T.P. Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. J. Psychopharmacol. (Oxford), 2004, 18(4), 457-474.
[] [PMID: 15582913]
Levin, E.D.; McClernon, F.J.; Rezvani, A.H. Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl.), 2006, 184(3-4), 523-539.
[] [PMID: 16220335]
Levin, E.D.; Conners, C.K.; Sparrow, E.; Hinton, S.C.; Erhardt, D.; Meck, W.H.; Rose, J.E.; March, J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.), 1996, 123(1), 55-63Berl.
[] [PMID: 8741955]
Singh, A.; Potter, A.; Newhouse, P. Nicotinic acetylcholine receptor system and neuropsychiatric disorders. IDrugs, 2004, 7(12), 1096-1103.
[PMID: 15599803]
Wilens, T.E.; Spencer, T.J.; Biederman, J. A review of the pharmacotherapy of adults with attention-deficit/hyperactivity disorder. J. Atten. Disord., 2002, 5(4), 189-202.
[] [PMID: 11967475]
Conners, C.K.; Levin, E.D.; Sparrow, E.; Hinton, S.C.; Erhardt, D.; Meck, W.H.; Rose, J.E.; March, J. Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacol. Bull., 1996, 32(1), 67-73.
[PMID: 8927677]
Gehricke, J.G.; Hong, N.; Whalen, C.K.; Steinhoff, K.; Wigal, T.L. Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder. Psychol. Addict. Behav., 2009, 23(4), 644-655.
[] [PMID: 20025370]
Poltavski, D.V.; Petros, T. Effects of transdermal nicotine on attention in adult non-smokers with and without attentional deficits. Physiol. Behav., 2006, 87(3), 614-624.
[] [PMID: 16466655]
Potter, A.S.; Newhouse, P.A. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol. Biochem. Behav., 2008, 88(4), 407-417.
[] [PMID: 18022679]
Potter, A.S.; Newhouse, P.A. Effects of acute nicotine administration on behavioral inhibition in adolescents with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.), 2004, 176(2), 182-194.
[] [PMID: 15083253]
Shytle, R.D.; Silver, A.A.; Wilkinson, B.J.; Sanberg, P.R. A pilot controlled trial of transdermal nicotine in the treatment of attention deficit hyperactivity disorder. World J. Biol. Psychiatry, 2002, 3(3), 150-155.
[] [PMID: 12478880]
Wilens, T.E.; Decker, M.W. Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition. Biochem. Pharmacol., 2007, 74(8), 1212-1223.
[] [PMID: 17689498]
Wilens, T.E.; Biederman, J.; Spencer, T.J.; Bostic, J.; Prince, J.; Monuteaux, M.C.; Soriano, J.; Fine, C.; Abrams, A.; Rater, M.; Polisner, D. A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder. Am. J. Psychiatry, 1999, 156(12), 1931-1937.
[PMID: 10588407]
Wilens, T.E.; Verlinden, M.H.; Adler, L.A.; Wozniak, P.J.; West, S.A. ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study. Biol. Psychiatry, 2006, 59(11), 1065-1070.
[] [PMID: 16499880]
Wilens, T.E.; Biederman, J.; Wong, J.; Spencer, T.J.; Prince, J.B. Adjunctive donepezil in attention deficit hyperactivity disorder youth: case series. J. Child Adolesc. Psychopharmacol., 2000, 10(3), 217-222.
[] [PMID: 11052411]
Biederman, J.; Mick, E.; Faraone, S.; Hammerness, P.; Surman, C.; Harpold, T.; Dougherty, M.; Aleardi, M.; Spencer, T. A double-blind comparison of galantamine hydrogen bromide and placebo in adults with attention-deficit/hyperactivity disorder: a pilot study. J. Clin. Psychopharmacol., 2006, 26(2), 163-166.
[] [PMID: 16633145]
Wilens, T.E.; Waxmonsky, J.; Scott, M.; Swezey, A.; Kwon, A.; Spencer, T.J.; Biederman, J. An open trial of adjunctive donepezil in attention-deficit/hyperactivity disorder. J. Child Adolesc. Psychopharmacol., 2005, 15(6), 947-955.
[] [PMID: 16379515]
Potter, A.S.; Dunbar, G.; Mazzulla, E.; Hosford, D.; Newhouse, P.A. AZD3480, a novel nicotinic receptor agonist, for the treatment of attention-deficit/hyperactivity disorder in adults. Biol. Psychiatry, 2014, 75(3), 207-214.
[] [PMID: 23856296]
Jucaite, A.; Öhd, J.; Potter, A.S.; Jaeger, J.; Karlsson, P.; Hannesdottir, K.; Boström, E.; Newhouse, P.A.; Paulsson, B. A randomized, double-blind, placebo-controlled crossover study of α4β 2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.), 2014, 231(6), 1251-1265.
[] [PMID: 23640072]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy