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Issues important for rational COMT inhibition.
Neurology. 2000; 55(11 Suppl 4):S24-7; discussion S28-32.Neur

Abstract

Levodopa is the most efficacious drug in the symptomatic treatment of Parkinson's disease. However, exogenously administered levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) so that only 1% of an administered dose gains access to the brain. Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa. Two COMT inhibitors, tolcapone and entacapone, have recently been introduced as adjuncts to levodopa to further inhibit peripheral levodopa metabolism and thereby enhance brain levodopa availability. This paper reviews the pharmacokinetics, dosing schedule, peripheral and central effects, and safety profile of these agents.

Authors+Show Affiliations

Jacor Research, Consultancy in Drug Development, Bottmingen, Switzerland.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11147507

Citation

Dingemanse, J. "Issues Important for Rational COMT Inhibition." Neurology, vol. 55, no. 11 Suppl 4, 2000, pp. S24-7; discussion S28-32.
Dingemanse J. Issues important for rational COMT inhibition. Neurology. 2000;55(11 Suppl 4):S24-7; discussion S28-32.
Dingemanse, J. (2000). Issues important for rational COMT inhibition. Neurology, 55(11 Suppl 4), S24-7; discussion S28-32.
Dingemanse J. Issues Important for Rational COMT Inhibition. Neurology. 2000;55(11 Suppl 4):S24-7; discussion S28-32. PubMed PMID: 11147507.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Issues important for rational COMT inhibition. A1 - Dingemanse,J, PY - 2001/1/9/pubmed PY - 2001/2/28/medline PY - 2001/1/9/entrez SP - S24-7; discussion S28-32 JF - Neurology JO - Neurology VL - 55 IS - 11 Suppl 4 N2 - Levodopa is the most efficacious drug in the symptomatic treatment of Parkinson's disease. However, exogenously administered levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) so that only 1% of an administered dose gains access to the brain. Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa. Two COMT inhibitors, tolcapone and entacapone, have recently been introduced as adjuncts to levodopa to further inhibit peripheral levodopa metabolism and thereby enhance brain levodopa availability. This paper reviews the pharmacokinetics, dosing schedule, peripheral and central effects, and safety profile of these agents. SN - 0028-3878 UR - https://www.unboundmedicine.com/medline/citation/11147507/Issues_important_for_rational_COMT_inhibition_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11147507.ui DB - PRIME DP - Unbound Medicine ER -