EFFECTS OF TOLCAPONE IN PARKINSONS PATIENTS TAKING L-DIHYDROXYPHENYLALANINE/CARBIDOPA AND SELEGILINE

A double-blind, placebo-controlled, crossover trial of tolcapone (RO 40-7592), 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.