Non-nicotinic neuropharmacological strategies for nicotine dependence: Beyond bupropion

Smoking is a major health problem and is propelled, at least in part, by the addictive properties of nicotine. Two types of pharmacological therapies have been approved for smoking cessation by the US Food and Drug Administration. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion (Zyban®), an atypical antidepressant, whose use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. This review focuses on recent advances that could lead to the development of improved novel pharmacological treatments. These strategies focus on altering reward processes in the brain by modulating various neurotransmitter systems: the most promising include dopamine D₃ receptor antagonists, noradrenaline reuptake inhibitors, GABA_B receptor agonists, metabotropic glutamate 5 (mGluR5) receptor antagonists, cannabinoid CB1 receptor antagonists, and corticotropin releasing factor (CRF) 1 receptor antagonists.