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.