Catechol-o-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients

J. W. Roberts, G. Cora-Locatelli, D. Bravi, M. A. Amantea, M. M. Mouradian, T. N. Chase

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopdcarbidopa in combination with single oral doses of tolcapone (Ro 40–7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopdcarbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safely reduce the wearing-off phenomenon associated with levodopdcarbidopa therapy.

Original languageEnglish (US)
Pages (from-to)2685-2688
Number of pages4
JournalNeurology
Volume43
Issue number12
DOIs
StatePublished - Dec 1993

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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