[Inhibition of the COMPT with entacapone in the treatment of motor fluctuations in Parkinson disease].

Abstract

Motor fluctuations are a common problem in the long-term treatment of Parkinson's disease (PD). Entacapone (Comtan) is a potent, peripherally acting, reversible and selective inhibitor of catechol-O-methyltransferase (COMT). Used as an adjuvant to levodopa therapy, entacapone slows the elimination of levodopa by decreasing peripheral conversion to 3-O-methyldopa, increasing central extracellular levodopa and striatal dopamine concentrations. Coadministered with levodopa/carbidopa or levodopa/benserazide, at doses of 200 mg 2 to 10 times daily in patients with end-of-dose fluctuations, entacapone may increase the duration of clinical response, both after the first single dose and after repeated dosing. At this dosage, it has a time to peak plasma concentration of 1.2 h and an elimination half life of 3.4 h. In two multicentric, long-term (24 weeks), parallel, randomized and placebo-controlled studies, entacapone increased the duration of 'on' time (by approximately 1 hour daily) and decreased the duration of 'off' time with a concomitant reduction in the mean daily levodopa dose. In these and other phase III studies, entacapone was generally well tolerated, with most adverse effects being dyskinesias and gastrointestinal disorders. Increased dyskinesia were generally controlled by reducing levodopa doses. Entacapone appears to be a useful adjunct in extending the benefit of each levodopa dose in PD patients with end-of-dose fluctuations.

• Authors: J Kulisevsky
• Journal: Neurologia (Barcelona, Spain) (Neurologia) 1999 Aug-Sep Vol. 14 Issue 7 Pg. 349-58 ISSN: 0213-4853 [Print] Spain
• Vernacular Title: Inhibición de la COMT con entacapone en el tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson.
• PMID: 10570622 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Antiparkinson Agents
• Catechols
• Enzyme Inhibitors
• Nitriles
• Levodopa
• entacapone
• Catechol O-Methyltransferase
• Carbidopa

Topics

• Aged
• Antiparkinson Agents (therapeutic use)
• Carbidopa (metabolism, therapeutic use)
• Catechol O-Methyltransferase (metabolism)
• Catechols (pharmacology, therapeutic use)
• Drug Therapy, Combination
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Humans
• Levodopa (metabolism, therapeutic use)
• Movement Disorders (drug therapy)
• Nitriles
• Parkinson Disease