R-(−)-1-(Benzofuran-2-yl)-2-propylaminopentane [(−)-BPAP] is a catecholaminergic and serotonergic activity enhancer that increases impulse-evoked catecholamine and serotonin release from nerve terminals, and is a candidate for symptomatic treatment of early Parkinson's disease. We now report the catecholamine and serotonin transporter-mediated actions of (−)-BPAP. The effects of (−)-BPAP on inhibition of neurotransmitter uptake and radioligand binding were assessed using human embryonic kidney 293 cells (HEK 293 cells) expressing cDNA for the human dopamine transporter (hDAT), norepinephrine transporter (hNET), and serotonin transporter (hSERT). The IC 50 values for the effects of (−)-BPAP on [3H]dopamine, [3H]norepinephrine, and [3H]serotonin uptake were 42±9, 52±19, and 640±120 nM, respectively. The IC 50 values for the effects of (−)-BPAP on [125I]3β-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester ([125I]RTI-55) binding to hDAT, hNET, and hSERT were 16±2, 211±61, and 638±63 nM, respectively. The effects of (−)-BPAP on spontaneous and tyramine-induced norepinephrine and dopamine release from rat brain synaptosomes using a superfusion system were also assessed. Tyramine but not (−)-BPAP potentiated norepinephrine release. Furthermore, (−)-BPAP inhibited tyramine-induced norepinephrine release. Thus, (−)-BPAP may block tyramine-induced adverse effects such as hypertensive crisis. The actions of (−)-BPAP on the spontaneous and tyramine-induced dopamine release resembled its effects on norepinephrine release. We conclude that (−)-BPAP is not only catecholaminergic and serotonergic activity enhancer, but also a norepinephrine and dopamine uptake inhibitor and a weak serotonin uptake inhibitor that does not possess a tyramine-like action on catecholamine release, and is an inhibitor of tyramine-induced release of norepinephrine.