THE EFFECTS OF THE COMT INHIBITOR ENTACAPONE ON HEMODYNAMICS AND PERIPHERAL CATECHOLAMINE METABOLISM DURING EXERCISE

1 Catechol-O-methyltransferase (COMT) inhibition might be assumed to p otentiate the effects of circulating catecholamines, particularly unde r conditions of enhanced catecholamine release. 2 The purpose of the p resent study was to establish whether the novel COMT inhibitor, entaca pone, changes haemodynamic responses and catecholamine metabolism duri ng 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 ergom eter, and blood pressure, heart rate and ECG were recorded. The concen trations of noradrenaline, adrenaline, DHPG (3,4-dihydroxyphenylglycol ), MHPG (3-methoxy-4-hydroxyphenyl-glycol) and, DOPAC (3,4-dihydroxyph enylacetic acid) in plasma were determined. 4 Entacapone did not influ ence haemodynamics or ECG at rest or during exercise. 5 Entacapone did not influence plasma catecholamine levels, either at rest or during e xercise. However, it altered the metabolic profile of catecholamines, which was shown by increases in the plasma concentrations of the monoa mine oxidase-dependent metabolites DHPG (by up to 100%) and DOPAC (by up to 53%), and by a decrease of the COMT-dependent metabolite MHPG (b y up to 29%).