The effect of COMT inhibition with entacapone on cardiorespiratory responses to exercise in patients with Parkinson's disease.
The inhibition of catechol-O-methyltransferase (COMT) may impair catecholamine clearance resulting in unwanted cardiac and hemodynamic events. We therefore studied the effects of entacapone, an inhibitor of peripheral COMT, on cardiorespiratory and plasma noradrenaline (NA) responses to exercise and on respiratory muscle strength in l-dopa treated patients with Parkinson's disease (PD). A randomized, double-blind, cross-over study with two 1week treatment periods was performed in 15 PD patients. The test battery included analysis of hemodynamics, gas exchange parameters and plasma NA during a maximal exercise test, assessment of maximal static airway pressures and pre- and post-exercise motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The first test was done after withholding l-dopa overnight ('run-in' test, off-phase). The second and third tests were done in on-phase after 1week treatment with either entacapone 200mg or placebo given with each dose of l-dopa. No differences in maximal work load, plasma NA, or in cardiorespiratory responses to either maximal or work rate standardized submaximal exercise were observed between entacapone and placebo, except for O(2) pulse, which was slightly lower (p < 0.05) after entacapone at submaximal exercise level. Maximal airway pressures were similar between the study treatments and run-in. Exercise had no effect on motor UPDRS after either study treatment or during the run-in test. No serious adverse events were observed. The results of this study suggest that entacapone does not change the work capacity, work efficiency or respiratory muscle strength in l-dopa treated PD patients with mild to moderate disease severity, and that its use with l-dopa seems to be safe in conditions of maximal physical effort. However, data from the long-term use of COMT inhibitors are needed to confirm these findings.
Lyytinen
J
J
Department of Neurology, University of Helsinki, P.O. Box 340, 00029 Helsinki, Finland. jukka.lyytinen@helsinki.fi
Kaakkola
S
S
Gordin
A
A
Kultalahti
E-R
ER
Teräväinen
H
H
Sovijärvi
A
A
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D009638:Norepinephrine