Levomilnacipran is an active enantiomer of the serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor milnacipran . It binds to the 5-HT and NE transporters (Kis = 11.2 and 92.2 nM, respectively, for human recombinant transporters) and inhibits reuptake in vitro (IC50s = 19 and 10.5 nM, respectively). It is selective for 5-HT and NE transporters over DAT (Ki = >10,000 nM for human recombinant DAT) and 23 receptors (Kis = ≥10,000 nM). Levomilnacipran increases extracellular levels of 5-HT and NE in rat cortex with minimal effective doses (MEDs) of 20 and 10 mg/kg, respectively. It decreases immobility in the forced swim and tail suspension tests (MEDs = 20 and 2.5 mg/kg, respectively) without increasing locomotor activity. Formulations containing levomilnacipran have been used in the treatment of major depressive disorder.