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Extending levodopa action

COMT inhibition

From the Department of Neurology (Dr. Martínez-Martín), Hospital Universitario de Getafe, Getafe (Madrid), Spain, and CNI Movement Disorders Center (Dr. O'Brien), Colorado Neurological Institute, Englewood, CO.

Address correspondence and reprint requests to Dr. Christopher F. O'Brien, CNI Movement Disorders Center, Colorado Neurological Institute, 701 E. Hampden Avenue, Suite 530, Englewood, CO 80110-2776.

Abstract.

Degradation of levodopa in the periphery is known to be associated with motor fluctuations and dyskinesia in Parkinson's disease (PD) patients. The enzyme catechol-O-methyltransferase (COMT) is responsible for much of this degradation. Therefore, inhibiting COMT activity is one method of extending the action of levodopa. The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally. COMT inhibitors increase patients' duration of response to levodopa and reduce response fluctuations. Administration may prolong levodopa-induced dyskinesia, but peak-dose dyskinesia does not appear to increase. To reduce dyskinesia, the total daily dose of levodopa can be reduced.