Pharmacological study of milnacipran, a novel antidepressant

Milnacipran ((±)-cis-1-phenyl-1-diethyl-aminocarbonyl-2-aminoethyl-cyclopropanehy drochloride) is a cyclopropane derivative newly developed by Pierre Fabre in France. The present study was undertaken to clarify the pharmacological characteristics of milnacipran compared with those of imipramine and of mianserin. Milnacipran potently decreased the duration of immobility in the behavioral despair test. In this test, no tolerance was observed after 7 consecutive days of treatment in rats. In addition, milnacipran clearly decreased the freezing behavior in the conditioned fear stress (CFS) test. Milnacipran enhanced 5-HTP induced head twitch behavior and yohimbine toxicity, and reversed reserpine induced hypothermia. Subchronic treatment with milnacipran did not change the numbers of β-adrenergic or 5-hydroxytryptamine₂ receptors in the rat cortex, whereas subchronic treatment with imipramine decreased both of these receptors. Like imipramine, milnacipran potently inhibited [³H]-paroxetine binding and [³H]-nisoxetine binding. These results suggest that milnacipran will be a novel antidepressant which is different from a typical antidepressant imipramine.