A novel potential antidepressant, AHR-9377, was evaluated for its inhibition of norepinephrine (NE), serotonin (5-HT) and dopamine (DA) reuptake in hypothalmic, cortical, and striatal rat synaptosomal preparations. AHR-9377 was found to be a potent, selective, noncompetitive inhibitor of NE reuptake. In addition, repeated injections of AHR-9377 caused a decrease in the density of beta adrenergic receptors in rat cerebral cortex. Little displacement by AHR-9377 at beta, alpha 1 and alpha 2 adrenergic, histaminergic, muscarinic, GABA-ergic, benzodiazepine of imipramine sites was observed. These pharmacological properties indicate that AHR-9377 may have clinical antidepressant activity with few side effects.