The effect of catechol-O-methyltransferase inhibition with entacapone on cardiovascular autonomic responses in L-Dopa-treated patients with Parkinson's disease

Clin Neuropharmacol. 2001 Jan-Feb;24(1):50-7. doi: 10.1097/00002826-200101000-00009.

Abstract

We have compared the effects of entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic responses in L-Dopa/dopa decarboxylase inhibitor-treated patients with Parkinson's disease (PD). In a double-blind, randomized, crossover study with two consecutive 1-week treatment periods, a battery of cardiovascular reflex tests (orthostatic, Valsalva, deep breathing, and isometric hand grip tests) was performed in a group of 15 patients with idiopathic PD. The first set of tests was performed after withholding L-Dopa overnight (control, "off" stage). The second and third sets of tests were performed in "on" stage after 1-week treatment with either entacapone 200 mg or placebo administered with each dose of L-Dopa/dopa decarboxylase (DDC) inhibitor. Valsalva, deep breathing, and orthostatic tests demonstrated no statistically significant differences in the ratio of the longest and shortest electrocardiographic R-to-R wave (R-R) intervals between entacapone and placebo or between study treatments and control. Blood pressure responses to both orthostatic challenge and prolonged isometric work (hand grip test) were similar between treatments. Systolic orthostatic hypotension was observed in only one patient during the control test, but it occurred more frequently after L-Dopa/DDC inhibitor, regardless of concomitant administration of either entacapone (n = 3) or placebo (n = 4). Peripheral COMT inhibition with entacapone does not significantly alter cardiovascular autonomic responses in L-Dopa-treated patients with PD.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiparkinson Agents / pharmacology*
  • Antiparkinson Agents / therapeutic use
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Catechol O-Methyltransferase / blood
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / pharmacology*
  • Catechols / therapeutic use
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Hand Strength / physiology
  • Heart Function Tests / drug effects*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Levodopa / pharmacology*
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Nitriles
  • Parkinson Disease / drug therapy
  • Parkinson Disease / enzymology*
  • Valsalva Maneuver / drug effects
  • Valsalva Maneuver / physiology

Substances

  • Antiparkinson Agents
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Nitriles
  • Levodopa
  • entacapone
  • Catechol O-Methyltransferase