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COMT Inhibitors in Parkinson's Disease

Published online by Cambridge University Press:  02 December 2014

Jean Rivest ,
C. Lynn Barclay  and
Oksana Suchowersky
Jean Rivest
Affiliation:
Centre Universitaire de Santé de l'Estrie, Fleurimont, Quebec
C. Lynn Barclay
Affiliation:
University of Ottawa, Ottawa, Ontario
Oksana Suchowersky
Affiliation:
University of Calgary, Calgary, Alberta
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Abstract

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The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson's medications. By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier. Pharmacokinetic studies have shown that both tolcapone and entacapone significantly prolong the elimination half life, and increase the area under the curve of levodopa without increasing C max. Clinical studies with COMT inhibitors have shown benefit in both stable and fluctuating PD patients with improvement in motor function with lower levodopa doses. Fluctuating patients also had increased “on” time and reduced “wearing off”. Side effects were most commonly related to increased dopaminergic stimulation. Specific side effects included diarrhea and elevated liver enzymes. The recent reports of three cases of fulminant hepatitis with the use of tolcapone has led many countries to remove this compound from their market. Concerns about a possible class effect should impose close monitoring of liver function tests with the use of any of the nitrocatechols.

Résumé

RÉSUMÉ

Inhibiteurs de la COMT dans la maladie de Parkinson. Les inhibiteurs de la COMT, le tolcapone et l'entacapone, appartiennent à une nouvelle classe de médicaments antiparkinsoniens. En inhibant l'enzyme catéchol-o-méthyl-transférase (COMT), ils empêchent la dégradation périphérique de la lévodopa permettant ainsi à des con-centrations plus élevées de traverser la barrière hémato-encéphalique. Des études de pharmacocinétique ont montré que le tolcapone et l' entacapone prolongent significativement la demi-vie et augmentent l'aire sous la courbe de la lévodopa sans augmenter le Cmax. Les études cliniques avec des inhibiteurs de la COMT ont montré des bénéfices tant chez les patients stables que chez ceux qui présentent des fluctuations, avec une amélioration de la fonction motrice avec des doses inférieures de lévodopa. Les patients fluctuants ont également présenté une augmentation du temps où ils sont fonctionnels et une diminution de la perte d'effet. Les effets secondaires étaient le plus souvent reliés à l'augmentation de la stimulation dopaminergique. La diarrhée et une élévation des enzymes hépatiques sont des effets secondaires spécifiques de ces médicaments. Trois cas d'hépatite fulminante avec le tolcapone ont incité plusieurs pays à retirer ce produit du marché. À cause de la possibilité qu'il s'agisse d'un effet de classe, on doit faire une surveillance étroite des épreuves de fonction hépatique dans l'utilisation de tous les nitrocatéchols.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 26 , Issue S2 , August 1999 , pp. S34 - S38
Copyright
Copyright © The Canadian Journal of Neurological 1999

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