Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease

Tolcapone is a selective peripheral and central catechol-O-methyltransferas e (COMT) inhibitor recently approved as adjunctive therapy in patients with idiopathic Parkinson's disease who are already being treated with a levodo paperipheral dopa decarboxylase inhibitor (DDI) combination. Tolcapone pote ntiates and prolongs the effect of levodopa in the central nervous system ( CNS) by enhancing levodopa's delivery to the CNS and slowing dopamine's cen tral metabolism. A short terminal disposition half-life of 2 hours mandates dosing 3 times/day. Dosage adjustment is generally unnecessary in the pres ence of mild to moderate renal and hepatic impairment. Coadministration of tolcapone with levodopa-DDI results in significant amelioration of the wear ing-off and on-off phenomena and frequently allows significant levodopa dos age reduction. In patients with stable disease, tolcapone improves "on" tim e. As might be expected from its potentiation of levodopa effects, dopamine rgic side effects are prominent with this agent. Although the main objectiv e of drug treatment in Parkinson's disease remains clinical improvement wit h an optimum dose and frequency of levodopa administration, tolcapone may p rove a useful adjunct to such therapy, especially in the presence of the we aring-off and on-off phenomena. The relative merits of this agent vis-a-vis dopamine receptor agonists are somewhat unclear at present. However, recen t guidelines from the American Academy of Neurology suggest that a COMT inh ibitor be added to levodopadopamine agonist therapy in patients with advanc ed disease.