Parkinson Disease: Leegwater-Kim J

Leegwater-Kim J, Waters C. · Lahey Clinic, Department of Neurology, 41 Mall Road, Burlington, MA 01805, USA. · Expert Rev Neurother. · Pubmed #18052761 No free full text.

Abstract: For decades, the cornerstone of treatment for Parkinson's disease (PD) has been levodopa, which provides a smooth clinical response early in the course of disease. However, many PD patients develop motor complications on long-term levodopa therapy. Catechol-O-methyltransferase (COMT) is a selective and widely distributed enzyme involved in the catabolism of levodopa. Tolcapone and entacapone are selective and potent COMT inhibitors that slow the metabolism of levodopa, thus prolonging its effects. While both drugs act peripherally, tolcapone also inhibits COMT in the CNS. Tolcapone has been shown to be an effective adjunct in the treatment of PD in Phase II and III clinical trials, improving motor fluctuations and reducing levodopa requirements. Rare reports of severe hepatotoxicity, however, limited tolcapone's implementation in the treatment of PD. A reappraisal of the data for tolcapone treatment in PD has found that this risk is very small if proper hepatic monitoring guidelines are followed. This article reviews the pharmacology and clinical data on tolcapone, with particular focus on drug safety and the future role of tolcapone therapy in the treatment of PD.

Leegwater-Kim J, Waters C. · Columbia University Medical Center, Department of Neurology, Division of Movement Disorders, 710 W. 168th Street, New York, NY 10032, USA. · Expert Opin Pharmacother. · Pubmed #17059382 No free full text.

Abstract: Although levodopa remains the gold standard treatment for Parkinson's disease, many patients develop motor complications with chronic levodopa exposure. Tolcapone is a catechol-O-methyltransferase inhibitor that extends the action of levodopa. When used in conjunction with levodopa, tolcapone has been shown to be effective in improving motor fluctuations and reducing levodopa requirements in Parkinson's disease patients. However, rare reports of severe hepatotoxicity have limited its use. A recent review of the data on tolcapone-treated patients suggests that, with proper monitoring of liver function, the potential for hepatotoxicity with tolcapone use is negligibly small.