Skip to main content

Advertisement

Log in

Pharmacotherapy for tobacco cessation: Nicotine agonists, antagonists, and partial agonists

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Nicotine replacement therapies (NRT) were the main pharmacologic option for treatment of nicotine dependence until the early 1990s, when controlled clinical trials confirmed the efficacy of bupropion, the first treatment not based on nicotine. Varenicline, a partial agonist at nicotine receptors, gained US regulatory approval in 2006 for smoking cessation. Although these agents are all effective for nicotine dependence, their efficacy rates vary compared with placebo (overall OR for NRT efficacy, 1.77; for bupropion, 1.94; for varenicline, 3.09). Each of these treatments has a place, sometimes in combinations with other agents, in cancer patients who continue to smoke. Our initial experience with varenicline has been encouraging. Bupropion has specific advantages for cancer patients, including increased energy, low risk for nausea, and decreased weight gain from quitting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Benowitz N: Pharmacology of nicotine: addiction and therapeutics. Ann Rev Pharmacol Toxicol 1996, 36:597–613. 1996.

    Article  CAS  Google Scholar 

  2. Nisell M, Marcus M, Nomikos GG, Svensson TH: Differential effects of acute and chronic nicotine on dopamine output in the core and shell of the rat nucleus accumbens. J Neural Transm 1997, 104:1–10.

    Article  PubMed  CAS  Google Scholar 

  3. Nomikos GG, Damsma G, Wenkstern D, Fibiger HC: Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis. Neuropsychopharmacology 1989, 2:273–279.

    Article  PubMed  CAS  Google Scholar 

  4. Pidoplichko VI, DeBiasi M, Williams JT, Dani JA: Nicotine activates and desensitizes midbrain dopamine neurons. Nature 1997, 390:401–404.

    Article  PubMed  CAS  Google Scholar 

  5. Robinson TE, Gorny G, Mitton E, Kolb B: Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex. Synapse 2001, 39:257–266.

    Article  PubMed  CAS  Google Scholar 

  6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, edn 4. Arlington, VA: American Psychiatric Association; 2000.

    Google Scholar 

  7. U.S. Department of Health and Human Services: Reducing Tobacco Use: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2000.

    Google Scholar 

  8. Kenford SL, Smith SS, Wetter DW, et al.: Predicting relapse back to smoking: contrasting affective and physical models of dependence. J Consul Clin Psychol 2002, 70:216–227.

    Article  Google Scholar 

  9. Summers KL, Giacobini E: Effects of local and repeated systemic administration of nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex. Neurochem Res 1995, 20753–20759.

  10. Hughes JR, Stead LF, Lancaster T: Antidepressants for smoking cessation. Cochrane Database Syst Rev 2003, CD000031.

  11. Gonzales D, Rennard SI, Nides M, et al.: Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006, 296:47–55.

    Article  PubMed  CAS  Google Scholar 

  12. Jorenby DE, Hays JT, Rigotti NA, et al.: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006, 296:56–63.

    Article  PubMed  CAS  Google Scholar 

  13. Hurt RD: Nicotine dependence—treatment for the 1990s. J Intern Med 1993, 233:307–310.

    Article  PubMed  CAS  Google Scholar 

  14. George TP, O’Malley SS: Current pharmacological treatments for nicotine dependence. Trends Pharmacol Sci 2004, 25:42–48.

    Article  PubMed  CAS  Google Scholar 

  15. Meert A, Mayer C, Milani MM, et al.: [Smoking cessation interventions among cancer patients]. Bull Cancer 2006, 93:363–369.

    PubMed  Google Scholar 

  16. Pontieri FE, Tanda G, Orzi F, DiChiara G: Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 1996, 382:255–257.

    Article  PubMed  CAS  Google Scholar 

  17. Izenwasser S, Cox BM: Inhibition of dopamine uptake by cocaine and nicotine: tolerance to chronic treatments. Brain Res 1992, 573:119–125.

    Article  PubMed  CAS  Google Scholar 

  18. Carr LA, Basham JK, York BK, Rowell PP: Inhibition of uptake of 1-methyl-4-phenylpyridinium ion and dopamine in striatal synaptosomes by tobacco smoke components. EurJ Pharmacol 1992, 215:285–287.

    Article  CAS  Google Scholar 

  19. Gourlay SG, McNeil JJ: Antismoking products. Med J Aust 1990, 153:699–707.

    PubMed  CAS  Google Scholar 

  20. Joseph AM, Norman SM, Ferry LH, et al.: The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996, 335:1792–1798.

    Article  PubMed  CAS  Google Scholar 

  21. Wilson K, Gibson N, Willan A, Cook D: Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies. Arch Intern Med 2000, 160:939–944.

    Article  PubMed  CAS  Google Scholar 

  22. Russell MA, Feyerabend C, Cole PV: Plasma nicotine levels after cigarette smoking and chewing nicotine gum. BMJ 1976, 1:1043–1046.

    PubMed  CAS  Google Scholar 

  23. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004, 3:CD000146.

  24. Henningfield JE, Radzius A, Cooper TM, Clayton RR: Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum. JAMA 1990, 264:1560–1564.

    Article  PubMed  CAS  Google Scholar 

  25. Hughes JR, Kottke T: Doctors helping smokers: real world tactics. Minn Med 1986, 69:293–295.

    PubMed  CAS  Google Scholar 

  26. Hughes JR, Hatsukami DK, Skoog KP: Physical dependence on nicotine in gum: a placebo substitution trial. JAMA 1986, 255:3277–3279.

    Article  PubMed  CAS  Google Scholar 

  27. Benowitz NL, Chan K, Denaro CP, Jacob P, III: Stable isotope method for studying transdermal drug absorption: the nicotine patch. Clin Pharmacol Ther 1991, 50:286–293.

    Article  PubMed  CAS  Google Scholar 

  28. Fiore MC, Jorenby DE, Baker TB, Kenford SL: Tobacco dependence and the nicotine patch: clinical guidelines for effective use. JAMA 1992, 268:2687–2694.

    Article  PubMed  CAS  Google Scholar 

  29. Kornitzer M, Boutsen M, Dramaix M, et al.: Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995, 24:41–47.

    Article  PubMed  CAS  Google Scholar 

  30. Russell MA, Jarvis MJ, Feyerabend C, Ferno O: Nasal nicotine solution: a potential aid to giving up smoking? BMJ (Clin Res Ed) 1983, 286:683–684.

    CAS  Google Scholar 

  31. Lunell E, Molander L, Ekberg K, Wahren J: Site of nicotine absorption from a vapour inhaler: comparison with cigarette smoking. Eur J Clin Pharmacol 2000, 55:737–741.

    Article  PubMed  CAS  Google Scholar 

  32. Blondal T, Gudmundsson LJ, Olafsdottir I, et al.: Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. BMJ 1999, 318:285–288.

    PubMed  CAS  Google Scholar 

  33. Bohadana A, Nilsson F, Rasmussen T, Martinet Y: Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2000, 160:3128–3134.

    Article  PubMed  CAS  Google Scholar 

  34. Tonnesen P, Mikkelsen KL: Smoking cessation with four nicotine replacement regimes in a lung clinic. Eur Respir J 2000, 16:717–722.

    Article  PubMed  CAS  Google Scholar 

  35. Choi JH, Dresler CM, Norton MR, Strahs KR: Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res 2003, 5:635–644.

    Article  PubMed  CAS  Google Scholar 

  36. Etter JF, Laszlo E, Zellweger JP, et al.: Nicotine replacement to reduce cigarette consumption in smokers who are unwilling to quit: a randomized trial. J Clin Psychopharmacol 2002, 22:487–495.

    Article  PubMed  CAS  Google Scholar 

  37. Bolliger CT, Zellweger JP, Danielsson T, et al.: Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety. BMJ 2000, 321:329–333.

    Article  PubMed  CAS  Google Scholar 

  38. Wennike P, Danielsson T, Landfeldt B, et al.: Smoking reduction promotes smoking cessation: results from a double blind, randomized, placebo-controlled trial of nicotine gum with 2-year follow-up. Addiction 2003, 98:1395–1402.

    Article  PubMed  Google Scholar 

  39. Rose JE, Behm FM, Westman EC: Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol 1998, 6:331–343.

    Article  PubMed  CAS  Google Scholar 

  40. Glover ED, Laflin MT, Schuh KJ, et al.: A randomized, controlled trial to assess the efficacy and safety of a transdermal delivery system of nicotine/mecamylamine in cigarette smokers. Addiction 2007, 102:795–802.

    Article  PubMed  Google Scholar 

  41. Ascher JA, Cole JO, Colin JN, et al.: Bupropion: a review of its mechanism of antidepressant activity. J Clin Psychiatry 1995, 56:395–401.

    PubMed  CAS  Google Scholar 

  42. Hughes JR, Stead LF, Lancaster T: Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007, CD000031.

  43. Slemmer JE, Martin BP, Damaj I: Bupropion is a nicotine antagonist. J Pharmacol Exp Ther 2000, 295:321–327.

    PubMed  CAS  Google Scholar 

  44. Damaj MI, Carroll FI, Eaton JB, et al.: Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors. Mol Pharmacol 2004, 66:675–682.

    Article  PubMed  CAS  Google Scholar 

  45. Vann RE, Rosecrans JA, James JR, et al.: Neurochemical and behavioral effects of bupropion and mecamylamine in the presence of nicotine. Brain Res 2006, 1117:18–24.

    Article  PubMed  CAS  Google Scholar 

  46. Cooper BR, Wang CM, Cox RF, et al.: Evidence that the acute behavioral and electrophysiological effects of bupropion (Wellbutrin) are mediated by a noradrenergic mechanism. Neuropsychopharmacology 1994, 11:133–141.

    PubMed  CAS  Google Scholar 

  47. Dong J, Blier P: Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment. Psychopharmacology 2001, 155:52–57.

    Article  PubMed  CAS  Google Scholar 

  48. Jorenby DE, Leischow SJ, Nides MA, et al.: A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999, 340:685–691.

    Article  PubMed  CAS  Google Scholar 

  49. Tutka P, Zatonski W: Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy. Pharmacol Rep 2006, 58:777–798.

    PubMed  CAS  Google Scholar 

  50. Etter JF: Cytisine for smoking cessation: a literature review and a meta-analysis. Arch Intern Med 2006, 166:1553–1559.

    Article  PubMed  CAS  Google Scholar 

  51. Coe JW, Brooks PR, Vetelino MG, et al.: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005, 48:3474–3477.

    Article  PubMed  CAS  Google Scholar 

  52. Tonstad S, Hays JT, Jorenby DE, et al.: Varenicline phase III studies; American Heart Association Scientific Sessions; Dallas, TX; 2005.

  53. Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at {alpha}4beta2 and a full agonist at {alpha}7 neuronal nicotinic receptors. Mol Pharmacol 2006, 70:801–805.

    Article  PubMed  CAS  Google Scholar 

  54. Gonzales DH, Rennard SI, Billing CB, et al.: A pooled analysis of varenicline, an alpha 4 beta 2 nicotinic receptor partial agonist vs bupropion, and placebo for smoking cessation. Annual Meeting of the Society of Research on Nicotine and Tobacco; Orlando, Florida; 2006.

  55. Tonstad S, Tonnesen P, Hajek P, et al.: Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006, 296:64–71.

    Article  PubMed  CAS  Google Scholar 

  56. Cappelleri JC, Baker CL, Bushmakin AG, Reeves K: Effects of varenicline on craving and withdrawal symptoms; 2006.

  57. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO: The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991, 86:1119–1127.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maher Karam-Hage.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karam-Hage, M., Cinciripini, P.M. Pharmacotherapy for tobacco cessation: Nicotine agonists, antagonists, and partial agonists. Curr Oncol Rep 9, 509–516 (2007). https://doi.org/10.1007/s11912-007-0072-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-007-0072-6

Keywords

Navigation