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Simultaneous inhibition of catechol-O-methyltransferase and monoamine oxidase A: effects on hemodynamics and catecholamine metabolism in healthy volunteers.
Clin Pharmacol Ther. 1996 Apr; 59(4):450-7.CP

Abstract

OBJECTIVE

To evaluate the effects of simultaneous pharmacologic inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase type A (MAO-A) on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during exercise.

BACKGROUND

Entacapone, a COMT inhibitor, is studied as an adjunct to levodopa treatment in patients with Parkinson's disease. Moclobemide, an MAO-A inhibitor, is already in clinical use as an antidepressant. It is likely that entacapone and moclobemide will be used concomitantly in the future in patients who have both Parkinson's disease and depression. It was therefore considered to be important to investigate the tolerability of combined COMT and MAO-A inhibition with entacapone and moclobemide.

DESIGN AND METHODS

This was a randomized, single-dose, double-blind crossover study of 12 healthy male volunteers. The treatments were either placebo, 200 mg entacapone, 150 mg moclobemide, or the combination of entacapone and moclobemide in single doses. Heart rate, blood pressure, impedance cardiography, and plasma concentrations of catecholamines and their metabolites were measured both at rest and during submaximal standardized bicycle exercise.

RESULTS

Entacapone and moclobemide (either alone or in combination) did not change heart rate, blood pressure, or any hemodynamic parameter at rest or during exercise compared with placebo. Neither were the concentrations of norepinephrine and epinephrine in plasma influenced. Both drugs had the expected effects on catecholamine metabolite concentrations in plasma. The decrease in the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) induced by moclobemide was not potentiated by entacapone.

CONCLUSION

The combined use of therapeutic single doses of entacapone and moclobemide in healthy volunteers did not affect the hemodynamics or concentrations of unconjugated norepinephrine and epinephrine in plasma. Other mechanisms are capable of regulating the concentrations of norepinephrine and epinephrine in circulating blood (and apparently also at receptors in the heart and vascular tissue) when both COMT and MAO-A activity are inhibited to a significant extent. This was also the case during marked sympathetic stimulation. The changes in the catecholamine metabolite concentrations provide evidence of effective COMT and MAO inhibition. Concentrations of MHPG in plasma are determined mainly by MAO-A activity because COMT inhibition did not have an additional effect on the moclobemide-induced decrease in plasma MHPG.

Authors+Show Affiliations

Orion Research Center, Orion-Farmos, Espoo, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

8612391

Citation

Illi, A, et al. "Simultaneous Inhibition of catechol-O-methyltransferase and Monoamine Oxidase A: Effects On Hemodynamics and Catecholamine Metabolism in Healthy Volunteers." Clinical Pharmacology and Therapeutics, vol. 59, no. 4, 1996, pp. 450-7.
Illi A, Sundberg S, Ojala-Karlsson P, et al. Simultaneous inhibition of catechol-O-methyltransferase and monoamine oxidase A: effects on hemodynamics and catecholamine metabolism in healthy volunteers. Clin Pharmacol Ther. 1996;59(4):450-7.
Illi, A., Sundberg, S., Ojala-Karlsson, P., Scheinin, M., & Gordin, A. (1996). Simultaneous inhibition of catechol-O-methyltransferase and monoamine oxidase A: effects on hemodynamics and catecholamine metabolism in healthy volunteers. Clinical Pharmacology and Therapeutics, 59(4), 450-7.
Illi A, et al. Simultaneous Inhibition of catechol-O-methyltransferase and Monoamine Oxidase A: Effects On Hemodynamics and Catecholamine Metabolism in Healthy Volunteers. Clin Pharmacol Ther. 1996;59(4):450-7. PubMed PMID: 8612391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous inhibition of catechol-O-methyltransferase and monoamine oxidase A: effects on hemodynamics and catecholamine metabolism in healthy volunteers. AU - Illi,A, AU - Sundberg,S, AU - Ojala-Karlsson,P, AU - Scheinin,M, AU - Gordin,A, PY - 1996/4/1/pubmed PY - 1996/4/1/medline PY - 1996/4/1/entrez SP - 450 EP - 7 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 59 IS - 4 N2 - OBJECTIVE: To evaluate the effects of simultaneous pharmacologic inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase type A (MAO-A) on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during exercise. BACKGROUND: Entacapone, a COMT inhibitor, is studied as an adjunct to levodopa treatment in patients with Parkinson's disease. Moclobemide, an MAO-A inhibitor, is already in clinical use as an antidepressant. It is likely that entacapone and moclobemide will be used concomitantly in the future in patients who have both Parkinson's disease and depression. It was therefore considered to be important to investigate the tolerability of combined COMT and MAO-A inhibition with entacapone and moclobemide. DESIGN AND METHODS: This was a randomized, single-dose, double-blind crossover study of 12 healthy male volunteers. The treatments were either placebo, 200 mg entacapone, 150 mg moclobemide, or the combination of entacapone and moclobemide in single doses. Heart rate, blood pressure, impedance cardiography, and plasma concentrations of catecholamines and their metabolites were measured both at rest and during submaximal standardized bicycle exercise. RESULTS: Entacapone and moclobemide (either alone or in combination) did not change heart rate, blood pressure, or any hemodynamic parameter at rest or during exercise compared with placebo. Neither were the concentrations of norepinephrine and epinephrine in plasma influenced. Both drugs had the expected effects on catecholamine metabolite concentrations in plasma. The decrease in the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) induced by moclobemide was not potentiated by entacapone. CONCLUSION: The combined use of therapeutic single doses of entacapone and moclobemide in healthy volunteers did not affect the hemodynamics or concentrations of unconjugated norepinephrine and epinephrine in plasma. Other mechanisms are capable of regulating the concentrations of norepinephrine and epinephrine in circulating blood (and apparently also at receptors in the heart and vascular tissue) when both COMT and MAO-A activity are inhibited to a significant extent. This was also the case during marked sympathetic stimulation. The changes in the catecholamine metabolite concentrations provide evidence of effective COMT and MAO inhibition. Concentrations of MHPG in plasma are determined mainly by MAO-A activity because COMT inhibition did not have an additional effect on the moclobemide-induced decrease in plasma MHPG. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/8612391/Simultaneous_inhibition_of_catechol_O_methyltransferase_and_monoamine_oxidase_A:_effects_on_hemodynamics_and_catecholamine_metabolism_in_healthy_volunteers_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9236&date=1996&volume=59&issue=4&spage=450 DB - PRIME DP - Unbound Medicine ER -