Serotonin uptake inhibition by the monoamine oxidase inhibitor brofaromine

The selective, reversible monoamine oxidase (MAO) A inhibitor brofaromine inhibits serotonin (5-HT) uptake in animal models in vitro and in vivo. We investigated whether such an effect can be demonstrated at clinical doses in humans by treating three groups of six volunteers with either placebo, 15 mg phenelzine three times a day, or 75 mg brofaromine twice a day in a 2-week experiment. As an indirect, although relevant parameter, binding of 3H-paroxetine to the 5-HT uptake sites on blood platelets was assessed. Moreover, whole-blood 5-HT as a measure of platelet 5-HT, and serum homovanillic acid (HVA) to tentatively estimate MAO inhibition, were determined. Brofaromine reduced 3H-paroxetine binding to platelets compared with placebo by 20%-25% throughout the treatment period, significance being reached on the last treatment day. In contrast, phenelzine tended to increase 3H-paroxetine binding. Both drugs increased whole-blood 5-HT to approximately 140%-150%. Brofaromine moderately and on some days significantly decreased serum HVA, whereas phenelzine only tended to do so. Our results suggest that brofaromine at the clinically used dosage of 150 mg/day does indeed inhibit 5-HT uptake, as evidenced by measurements of 3H-paroxetine binding to platelets.