Simultaneous inhibition of catecholamine-O-methylation by entacapone and neuronal uptake by imipramine: Lack of interactions

Objective: We have evaluated the effects of simultaneous inhibition of catechol-O-methyltransferase (COMT) by entacapone and of neuronal monoamine reuptake by imipramine on haemodynamics and catecholamine metabolism, and the safety and tolerability of the drug combination in healthy women. Methods: In a randomized, single-dose, single-blind, cross-over study, 12 healthy women were given placebo, entacapone (200 mg), imipramine (75 mg) or entacapone and imipramine in combination. Heart rate, blood pressure, systolic time intervals, and plasma concentrations of catecholamines and their metabolites were measured at rest and during exercise. Results: The only drug-related effect on haemodynamics was an increase in heart rate during exercise after imipramine. The increase in heart rate after the combination of entacapone and imipramine was similar to that after imipramine alone. Entacapone alone had no effects on haemodynamics. Imipramine and entacapone had no significant effects on the plasma concentrations of noradrenaline and adrenaline. No interactions between entacapone and imipramine were detected.