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01-02-2015 | Review Article

Catechol-O-Methyltransferase Inhibitors in Parkinson’s Disease

Author: Thomas Müller

Published in: Drugs | Issue 2/2015

Abstract

Inhibitors of catechol-O-methyltransferase (COMT) are commonly used as an adjunct to levodopa in patients with Parkinson’s disease (PD) for the amelioration of wearing-off symptoms. This narrative review aims to discuss the role of COMT inhibitors on peripheral levodopa metabolism and continuous brain delivery of levodopa, and to describe their metabolic properties. Oral application of levodopa formulations with a dopa decarboxylase inhibitor (DDI) results in fluctuating levodopa plasma concentrations, predominantly due to the short half-life of levodopa and its slowing of gastric emptying. Following transport across the blood–brain barrier and its metabolic conversion to dopamine, these peripheral ‘ups and downs’ of levodopa are reflected in fluctuating dopamine levels in the synaptic cleft between presynaptic and postsynaptic dopaminergic neurons of the nigrostriatal system. As a result, pulsatile postsynaptic dopaminergic stimulation takes place and results in the occurrence of motor complications, such as wearing-off and dyskinesia. More continuous plasma behaviour was observed after the combination of levodopa/DDI formulations with COMT inhibitors. These compounds also weaken a levodopa/DDI-related homocysteine increase, as biomarker for an impaired methylation capacity, which is involved in an elevated oxidative stress exposure. These findings favour the concept of chronic levodopa/DDI application with concomitant inhibition of COMT and monoamine oxidase, since deamination of dopamine via this enzyme also generates free radicals. This triple combination is suggested as standard levodopa application in patients with PD who need levodopa, if they will tolerate it.

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Title: Catechol-O-Methyltransferase Inhibitors in Parkinson’s Disease
Author: Thomas Müller
Publication date: 01-02-2015
Publisher: Springer International Publishing
Published in: Drugs / Issue 2/2015
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-014-0343-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Catechol-O-Methyltransferase Inhibitors in Parkinson’s Disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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