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The effects of the COMT inhibitor entacapone on haemodynamics and peripheral catecholamine metabolism during exercise.

1. Catechol-O-methyltransferase (COMT) inhibition might be assumed to potentiate the effects of circulating catecholamines, particularly under conditions of enhanced catecholamine release. 2. The purpose of the present study was to establish whether the novel COMT inhibitor, entacapone, changes haemodynamic responses and catecholamine metabolism during exercise. 3. Entacapone was given orally to 12 healthy male subjects (age 23-30 years) in increasing single doses from 0 mg (control day) to 200 mg. A submaximal exercise test was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of noradrenaline, adrenaline, DHPG (3,4-dihydroxyphenylglycol), MHPG (3-methoxy-4-hydroxyphenyl-glycol) and, DOPAC (3,4-dihydroxyphenylacetic acid) in plasma were determined. 4. Entacapone did not influence haemodynamics or ECG at rest or during exercise. 5. Entacapone did not influence plasma catecholamine levels, either at rest or during exercise. However, it altered the metabolic profile of catecholamines, which was shown by increases in the plasma concentrations of the monoamine oxidase-dependent metabolites DHPG (by up to 100%) and DOPAC (by up to 53%), and by a decrease of the COMT-dependent metabolite MHPG (by up to 29%).