Effects of tolcapone in Parkinson's patients taking L‐dihydroxyphenylalanine/carbidopa and selegiline

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Abstract
A double‐blind, placebo‐controlled, crossover trial of tolcapone (RO 407592), a potent reversible inhibitor of catechol‐O‐methyltransferase (COMT), was performed in 10 Parkinson's disease (PD) patients to determine single‐dose safety and efficacy. All subjects were chronically treated with stable doses of selegiline and L‐dihydroxyphenylalanine (L‐DOPA)/carbidopa. Tolcapone was administered in four single ascending doses (50‐800 mg) randomly paired with placebo. Motor ratings were performed every 30 min for 6 h. At higher doses (400 mg and 800 mg), tolcapone prolonged the antiparkinson response of L‐DOPA. Nausea was the most common adverse effect of the tolcapone—L‐DOPA/carbidopa—selegiline combination. Adverse cardiovascular effects were not seen. The acute inhibition of amino acid decarboxylase, monoamine oxidase‐B, and COMT is well tolerated and prolongs the L‐DOPA response in PD patients. Tolcapone may be a safe and useful adjunct to L‐DOPA/carbidopa in PD patients taking selegiline.

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