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

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.