Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl) 
is a nonselective inhibitor of the dopamine transporter (DAT) and the 
norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic 
acetylcholine receptors (nAChRs). In animal models used commonly to screen for 
antidepressant activity, bupropion shows a positive response. Also using animal 
models, bupropion has been shown to attenuate nicotine-induced unconditioned 
behaviors, to share or enhance discriminative stimulus properties of nicotine 
and to have a complex effect on nicotine self-administration, i.e., low doses 
augmenting nicotine self-administration and high doses attenuating 
self-administration. Current studies show that bupropion facilitates the 
acquisition of nicotine conditioned place preference in rats, further suggesting 
that bupropion enhances the rewarding properties of nicotine. Bupropion has been 
shown to attenuate the expression of nicotine withdrawal symptoms in both animal 
models and human subjects. With respect to relapse, current studies show that 
bupropion attenuates nicotine-induced reinstatement in rats, but large 
individual differences are apparent. Clinically, bupropion is used as a 
treatment for two indications, as an antidepressant, the indication for which it 
was developed, and as a tobacco use cessation agent. In clinical trials, 
bupropion is being tested as a candidate treatment for psychostimulant drug 
abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is 
available in three bioequivalent oral formulations, immediate release (IR), 
sustained release (SR), and extended release (XL). Extensive hepatic metabolism 
of bupropion produces three pharmacologically active metabolites, which may 
contribute to its clinical profile.