Amitifadine

Amitifadine (am-i-TIF-a-deen) (DOV-21,947 or EB-1010) is an antidepressant drug being developed by Euthymics Bioscience Inc. It is a so-called triple reuptake inhibitor (TRI) or serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).

It is the (+)-enantiomer of DOV-216,303, and its (−)-enantiomer is DOV-102,677. K_i values for SERT, NET, and DAT are 99 nM, 262 nM, and 213 nM. The IC₅₀ values for serotonin, norepinephrine and dopamine uptake are 12, 23 and 96 nM, respectively

Amitifadine reduces the duration of immobility in the forced swim test in rats with an oral minimum effective dose (MED) of 5 mg/kg. This antidepressant-like effect manifests in the absence of significant increases in motor activity at doses of up to 20 mg/kg. Amitifadine also produces a dose-dependent reduction in immobility in the tail suspension test, with an oral MED of 5 mg/kg. In microdialysis studies, amitifadine increased extracellular levels of serotonin, norepinephrine and dopamine in brain regions and did not induce hyperactivity in rats. Results in a small clinical trial indicated that amitifadine had statistically significant antidepressant effects and was well tolerated.