title: Neurochemical and psychotropic effects of bupropion in healthy male subjects.
abstract: 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.
authors.affiliation: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
authors.forename: Susan
authors.initials: S
authors.lastname: Slater
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boucher
authors.forename: Guy
authors.initials: G
authors.lastname: Debonnel
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016642:Bupropion / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011619:Psychotropic Drugs; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D016642:Bupropion; D012701:Serotonin