The effects of the COMT inhibitor nitecapone for one week on exercise haemodynamics and catecholamine disposition.
We have studied resting and exercise haemodynamics and catecholamine disposition after catechol-O-methyl-transferase (COMT) inhibition with nitecapone 100 mg t.d.s. for 7 days in 15 healthy men (aged 21 to 28 y) in a placebo-controlled, cross-over study. Nitecapone did not alter resting or exercise heart rates, blood pressure, or plasma catecholamine concentrations, but it altered the metabolic profile of endogenous catecholamines, as shown by: (1) a fall in the concentrations of the COMT-dependent metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) by 22% (P < 0.01), (2) increases in plasma concentrations of the monoamine oxidase-dependent metabolites 3,4-dihydroxyphenylglycol (DHPG) by up to 90% (P < 0.001) and 3,4-dihydroxyphenylacetic acid (DOPAC) by 67% (P < 0.05), (3) a three-fold increase in the concentration of circulating conjugated adrenaline (P < 0.001).
Sundberg
S
S
Research Center, Orion Pharmaceutica, Espoo, Finland.
Scheinin
M
M
Ojala-Karlsson
P
P
Akkila
J
J
Gordin
A
A
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010422:Pentanones / Q000494:pharmacology*; D005082:Physical Exertion; D013997:Time Factors
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D010422:Pentanones; C057364:nitecapone; D009638:Norepinephrine; D004837:Epinephrine