Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Linda P Dwoskin; Anthony S Rauhut; Kelley A King‐Pospisil; Michael T Bardo

doi:10.1111/j.1527-3458.2006.00178.x

. 2007 Jan 11;12(3-4):178–207. doi: 10.1111/j.1527-3458.2006.00178.x

Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Linda P Dwoskin ^1,^2,^✉, Anthony S Rauhut ³, Kelley A King‐Pospisil ², Michael T Bardo ⁴

PMCID: PMC6506196 PMID: 17227286

ABSTRACT

Bupropion hydrochloride ((±)‐2‐tert‐butylamino)‐3′‐chloropropiophenone · 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.

Keywords: Antidepressants, Bupropion, Neurotransmitter transporter inhibitors, Nicotinic receptor antagonists, Tobacco use cessation, Wellbutrin®, Zyban®

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Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Linda P Dwoskin

Anthony S Rauhut

Kelley A King‐Pospisil

Michael T Bardo

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Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent

Linda P Dwoskin

Anthony S Rauhut

Kelley A King‐Pospisil

Michael T Bardo

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