Tolcapone (TN)

Tolcapone is a selective, potent and reversible nitro catechol type inhibitor of enzyme catechol-O-methyl transferase (COMT). Tolcapone binds to the catalytic center of COMT in both peripheral and central nervous systems with greater affinity than any of the three catecholamine, including Levodopa (L-DOPA). It thereby prevents the 3-0-methylation of L-DOPA (3-hydroxy-L-tyrosine) by COMT which produces 3-0-methyldopa (3-methyoxy-l-tyrosine), a major metabolite that competes with L-DOPA to cross the blood-brain barrier. Thus Tolcapone improves the bioavailability and reduces the clearance of L-DOPA and subsequently dopamine from the central nervous system (CNS). Tolcapone is administered adjunct with Levodopa and AADC because it increases the bioavailability of L-DOPA.[9] Since Tolcapone has a greater affinity for COMT, it inhibits the enzyme from methylating levodopa.