History and Discovery | Structure–Activity Relations | Pharmacological Profile | Pharmacokinetics and Disposition | Mechanism of Action | Indications and Efficacy | Side Effects and Toxicology | Drug–Drug Interactions | Conclusion | References
Bupropion was discovered more than 40 years ago when investigators
were searching for an antidepressant with a novel mechanism of action
and safer side-effect profile. Synthesized in 1966, this unique
compound, different from tricyclic antidepressants (TCAs) and monoamine oxidase
inhibitors (MAOIs), was found to have antidepressant activity in
animal models that are predictive of antidepressant activity in
humans (Soroko and Maxwell 1983). Bupropion was discovered
to have minimal sympathomimetic and anticholinergic side effects
and a safer pharmacological and biochemical profile in comparison with
other antidepressants. Although both bupropion and selective serotonin
reuptake inhibitors (SSRIs) were developed with similar goals in
mind, their mechanisms of action are unique (Hudziak and Rettew 2004; Soroko and Maxwell 1983). Bupropion is
classified as an aminoketone antidepressant (Mehta 1983).
Its mechanism of action is thought to be via dual inhibition of
norepinephrine and dopamine reuptake (NDRI) without clinically significant
serotonin reuptake inhibition (Horst and Preskorn 1998; Stahl et al. 2004). Both bupropion and SSRIs appear to be equally
efficacious in the treatment of major depression (Feighner et al. 1991). The sustained-release (bupropion SR) formulation,
approved in 1996, has also proved to be significantly better than
placebo in preventing depression relapse (Weihs et al. 2002).
Bupropion's tolerability is superior to that of SSRIs,
with minimal effects on weight, less sedation, minimal withdrawal
symptoms upon discontinuation, and fewer or no sexual side effects (Thase et al. 2005).