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Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease.
Int Rev Neurobiol. 2010; 95:207-25.IR

Abstract

Entacapone and tolcapone are reversible COMT inhibitors which have been approved for clinical use in patients with Parkinson disease (PD). Nebicapone is a third COMT inhibitor which has been studied in humans. COMT inhibitors are used in combination with levodopa and a dopa decarboxylase (DDC) inhibitor. Each of them has problems either in pharmacokinetics, pharmacodynamics, clinical efficacy, or in safety. All three inhibitors have short elimination half-lives, about 2-3h. Tolcapone is longer acting and more potent COMT inhibitor than entacapone; nebicapone lies in between. However, none of the present inhibitors cause a complete peripheral COMT inhibition. Tolcapone and nebicapone have increased more levodopa AUC than entacapone which is reflected also in their clinical efficacy. The most common adverse event with COMT inhibitors is dyskinesia which is usually managed by decreasing levodopa dose. The greatest problem with tolcapone and probably also with nebicapone is their liver toxicity which is not seen with entacapone. Tolcapone causes severe diarrhea more often than entacapone. Though the present COMT inhibitors have improved significantly the treatment of advanced PD patients, they still have several problems and weaknesses leaving room for developing better COMT inhibitors.

Authors+Show Affiliations

Department of Neurology, University of Helsinki, Helsinki, Finland.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21095464

Citation

Kaakkola, Seppo. "Problems With the Present Inhibitors and a Relevance of New and Improved COMT Inhibitors in Parkinson's Disease." International Review of Neurobiology, vol. 95, 2010, pp. 207-25.
Kaakkola S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease. Int Rev Neurobiol. 2010;95:207-25.
Kaakkola, S. (2010). Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease. International Review of Neurobiology, 95, 207-25. https://doi.org/10.1016/B978-0-12-381326-8.00009-0
Kaakkola S. Problems With the Present Inhibitors and a Relevance of New and Improved COMT Inhibitors in Parkinson's Disease. Int Rev Neurobiol. 2010;95:207-25. PubMed PMID: 21095464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson's disease. A1 - Kaakkola,Seppo, PY - 2010/11/25/entrez PY - 2010/11/26/pubmed PY - 2011/3/8/medline SP - 207 EP - 25 JF - International review of neurobiology JO - Int Rev Neurobiol VL - 95 N2 - Entacapone and tolcapone are reversible COMT inhibitors which have been approved for clinical use in patients with Parkinson disease (PD). Nebicapone is a third COMT inhibitor which has been studied in humans. COMT inhibitors are used in combination with levodopa and a dopa decarboxylase (DDC) inhibitor. Each of them has problems either in pharmacokinetics, pharmacodynamics, clinical efficacy, or in safety. All three inhibitors have short elimination half-lives, about 2-3h. Tolcapone is longer acting and more potent COMT inhibitor than entacapone; nebicapone lies in between. However, none of the present inhibitors cause a complete peripheral COMT inhibition. Tolcapone and nebicapone have increased more levodopa AUC than entacapone which is reflected also in their clinical efficacy. The most common adverse event with COMT inhibitors is dyskinesia which is usually managed by decreasing levodopa dose. The greatest problem with tolcapone and probably also with nebicapone is their liver toxicity which is not seen with entacapone. Tolcapone causes severe diarrhea more often than entacapone. Though the present COMT inhibitors have improved significantly the treatment of advanced PD patients, they still have several problems and weaknesses leaving room for developing better COMT inhibitors. SN - 2162-5514 UR - https://www.unboundmedicine.com/medline/citation/21095464/Problems_with_the_present_inhibitors_and_a_relevance_of_new_and_improved_COMT_inhibitors_in_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/B978-0-12-381326-8.00009-0 DB - PRIME DP - Unbound Medicine ER -