Monoamine uptake inhibition by plasma from healthy volunteers after single oral doses of the antidepressant milnacipran.

Abstract

In a placebo-controlled double-blind cross-over study, we gave 12 healthy male volunteers placebo or milnacipran orally, such that each volunteer received placebo and two doses of milnacipran. Blood samples taken before and at various times after dosing were analysed for plasma concentrations of unchanged milnacipran and the inhibitory effect of the plasma on the uptake of 3H-5-hydroxytryptamine (5HT) into normal human platelets or of 3H-noradrenaline into rat hypothalamus homogenate. The mean maximal inhibition of 5HT and noradrenaline uptake was correlated with drug dose. The inhibition of 5HT uptake was correlated with the inhibition of noradrenaline uptake and both were correlated with plasma concentration of unchanged drug at all times and doses tested. Thus, milnacipran, when given orally to man, circulates in a biologically active form with similar potency for the inhibition of 5HT and noradrenaline uptake.