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COMT inhibition in the treatment of Parkinson's disease.
J Neurol. 1998 Nov; 245(11 Suppl 3):P25-34.JN

Abstract

A new approach in the treatment of Parkinson's disease is the inhibition of catechol-O-methyltransferase (COMT) with new generation COMT inhibitors, entacapone and tolcapone. Entacapone acts mainly peripherally whereas tolcapone acts both peripherally and centrally. They induce a dose-dependent inhibition of COMT activity in erythrocytes and a significant decrease in the plasma levels of 3-O-methyldopa, indicating their effectiveness as COMT inhibitors. Consequently, they increase the elimination half-life of levodopa and thus prolong the availability of levodopa to the brain without significantly affecting the Cmax or tmax of levodopa. Clinically, the improved levodopa availability is seen as prolonged motor response to levodopa/DDC inhibitor and also as prolonged duration of dyskinesias in Parkinson's disease patients with end-of-dose fluctuations. The dyskinesias are managed by decreasing the daily levodopa dose in Parkinson's disease patients with end-of-dose fluctuations. Both pharmacokinetically and clinically the 200-mg dose of entacapone is the most effective dose compared with placebo. For tolcapone 100 and 200 mg have most often proved to be the optimal doses. Based on the duration of COMT inhibition entacapone is administered with each levodopa/DDC inhibitor dose whereas tolcapone is given three times daily. Both entacapone and tolcapone are well-tolerated. However, there seems to be a trend for tolcapone to induce more often diarrhoea and increase in liver transaminases compared with entacapone. Thus, COMT inhibitors are clinically significant and beneficial adjunct to levodopa therapy in Parkinson's disease patients with end-of-dose fluctuations. Their effects and significance also in the treatment of de novo patients need to be clarified.

Authors+Show Affiliations

Department of Neurology, University of Turku, Finland.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

9808337

Citation

Ruottinen, H M., and U K. Rinne. "COMT Inhibition in the Treatment of Parkinson's Disease." Journal of Neurology, vol. 245, no. 11 Suppl 3, 1998, pp. P25-34.
Ruottinen HM, Rinne UK. COMT inhibition in the treatment of Parkinson's disease. J Neurol. 1998;245(11 Suppl 3):P25-34.
Ruottinen, H. M., & Rinne, U. K. (1998). COMT inhibition in the treatment of Parkinson's disease. Journal of Neurology, 245(11 Suppl 3), P25-34.
Ruottinen HM, Rinne UK. COMT Inhibition in the Treatment of Parkinson's Disease. J Neurol. 1998;245(11 Suppl 3):P25-34. PubMed PMID: 9808337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - COMT inhibition in the treatment of Parkinson's disease. AU - Ruottinen,H M, AU - Rinne,U K, PY - 1998/11/10/pubmed PY - 1998/11/10/medline PY - 1998/11/10/entrez SP - P25 EP - 34 JF - Journal of neurology JO - J Neurol VL - 245 IS - 11 Suppl 3 N2 - A new approach in the treatment of Parkinson's disease is the inhibition of catechol-O-methyltransferase (COMT) with new generation COMT inhibitors, entacapone and tolcapone. Entacapone acts mainly peripherally whereas tolcapone acts both peripherally and centrally. They induce a dose-dependent inhibition of COMT activity in erythrocytes and a significant decrease in the plasma levels of 3-O-methyldopa, indicating their effectiveness as COMT inhibitors. Consequently, they increase the elimination half-life of levodopa and thus prolong the availability of levodopa to the brain without significantly affecting the Cmax or tmax of levodopa. Clinically, the improved levodopa availability is seen as prolonged motor response to levodopa/DDC inhibitor and also as prolonged duration of dyskinesias in Parkinson's disease patients with end-of-dose fluctuations. The dyskinesias are managed by decreasing the daily levodopa dose in Parkinson's disease patients with end-of-dose fluctuations. Both pharmacokinetically and clinically the 200-mg dose of entacapone is the most effective dose compared with placebo. For tolcapone 100 and 200 mg have most often proved to be the optimal doses. Based on the duration of COMT inhibition entacapone is administered with each levodopa/DDC inhibitor dose whereas tolcapone is given three times daily. Both entacapone and tolcapone are well-tolerated. However, there seems to be a trend for tolcapone to induce more often diarrhoea and increase in liver transaminases compared with entacapone. Thus, COMT inhibitors are clinically significant and beneficial adjunct to levodopa therapy in Parkinson's disease patients with end-of-dose fluctuations. Their effects and significance also in the treatment of de novo patients need to be clarified. SN - 0340-5354 UR - https://www.unboundmedicine.com/medline/citation/9808337/COMT_inhibition_in_the_treatment_of_Parkinson's_disease_ L2 - https://dx.doi.org/10.1007/pl00007743 DB - PRIME DP - Unbound Medicine ER -