Behavioural and pharmacological mechanisms of bupropion's anti-smoking effects: recent preclinical and clinical insights.

Ongoing studies continue to explore the behavioural and pharmacological effects of bupropion in smoking cessation studies and animal models of nicotine dependence. In the present review, the components of nicotine dependence that form the most likely targets of bupropion are identified within the context of an expanding preclinical and clinical literature regarding the anti-addictive properties of bupropion. Second, preclinical and clinical data that implicate specific pharmacological modes of action of bupropion in mediating the anti-smoking effects of the compound are discussed. Third, it is suggested that the unique mixed pharmacological profile of bupropion provides (1) attenuation of the multiple negative consequences of withdrawal via blockade of dopamine and noradrenaline reuptake; (2) replacement of the reward-facilitating and subjective effects of nicotine via blockade of dopaminergic reuptake; (3) attenuation of the rewarding effects of acute nicotine by nicotinic acetylcholine receptor blockade. The importance of species differences in bupropion metabolism in the interpretation of preclinical studies is highlighted. Finally, future studies are suggested to address identified gaps in the knowledge: most importantly, to provide stronger evidence for the role of noradrenaline reuptake inhibition in bupropion-induced attenuation of nicotine withdrawal. Future studies aimed at providing more evidence for the three-fold nature of the anti-smoking effects of bupropion are also suggested, along with the possibility of utilizing adjunct therapies to improve smoking cessation rates.