Neurochemical and psychotropic effects
of bupropion in healthy male subjects

Gobbi G, Slater S, Boucher N, Debonnel G, Blier P.
*Neurobiological Psychiatry Unit,
Department of Psychiatry,
McGill University, Montreal, Canada;
and Department of Psychiatry,
McKnight Brain Institute,
University of Florida,
Gainesville, Florida, USA.
J Clin Psychopharmacol. 2003 Jun;23(3):233-9


Bupropion is a weak inhibitor of noradrenaline (NE) and dopamine (DA) reuptake and has no direct action on serotonin (5-HT) neuronal elements. In the rat brain, bupropion suppresses NE neuron firing activity via the activation of alpha(2)-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons. Twenty-five healthy young male volunteers, with no previous history of psychiatric disorders, were randomized to one of four 7-day regimens: placebo, bupropion (150 mg) once daily, bupropion (150 mg) twice a day, and methylphenidate SR (20 mg daily). To assess the activity of the NE reuptake process, the blood pressure response to intravenous tyramine was determined. A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition. Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration, with a decrease serving as an index of 5-HT reuptake blockade. The Profile of Mood States (POMS) scale was used to assess behavioral and psychological changes. Neither bupropion nor methylphenidate altered the tyramine pressor response, in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors. Neither drug modified 5-HT concentrations. However, POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness, agreeability, and energy, whereas 300 mg/day improved only attention. In contrast, methylphenidate improved only energy. These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans. Presumably it enhances synaptic availability of NE by increasing release. Yet, because its behavioral profile is different from that of methylphenidate, it may not share all the biochemical properties of psychostimulants.
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