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Bupropion appears to enhance monoaminergic neurotransmission via its effects on both the NE and DA transporterswith subsequent reuptake inhibition of these 2 neurotransmittersBupropion and 2 of its metaboliteshydroxybupropion and threohydrobupropionwere shown to decrease the uptake of NE and DA into rat and mouse synaptosomes9 Bupropion’s activity as a DA transporter inhibitor is further supported by a recent study showing approximately a 3-fold increase in expression of the immediate early gene c-fos in human DA transporter cellsandif coincubated with DAan attenuation of the DA-induced c-fos in human DA transporter cells14 Acute administration of bupropion reduces firing of brain stem NE and DA neuronsdata on fileGlaxoSmithKlineResearch Triangle ParkN.CAdditionallyfiring rates of NE neurons in the locus ceruleus are inhibited after acute bupropion administration9 Microdialysis studies following acute administration of bupropion demonstrate that extra-cellular NE and DA concentrations are increased in the nucleus accumbensdata on fileGlaxoSmithKlineResearch Triangle ParkN.CFurther evidence of the NDRI action of bupropion was found when administration of NEor DA-blocking drugs was shown to reduce the efficacy of bupropionand hydroxybupropionin animal models of depression15.

Adverse events leading to treatment discontinuation with ZybanRincluded tremorsand rashesThe most commonly observed adverse reactions were dry mouth and insomniaSmoking cessation is often associated with nicotine withdrawal symptomssome of which are also recognized as adverse events associated with bupropionRef]

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