A powerful catechol-o-mEthyl-transfErase (comt) inhibitor medication that delays the action of the enzyme catechol-o-METHYLTRANSFERASE (COMT) to metabolize LEVODOPA into 3-O-methyldopa (3-OMD) in the bloodstream, extending the amount of levodopa that crosses the blood-brain barrier to be metabolized into dopamine in the brain. COMT is also present in the brain to convert dopamine to 3-methoxytyramine (3-MT), so COMT inhibition probably also extends the life of dopamine inside the brain. Tolcapone (Tasmar) was the first COMT inhibitor marketed, after its U.S. Food and Drug Administration (FDA) approval in the United States in 1993. It marked a major advance in medication treatment for Parkinson’s disease, allowing people with Parkinson’s to take lower and less frequent dosages of levodopa and derive greater benefit from them.
Tolcapone is effective as one of the adjunct therapies used in middle to late stages of the disease when increasingly higher dosages of levodopa are required to relieve symptoms. Side effects include diarrhea and dyskinEsias. Rarely tolcapone can cause serious and sometimes fatal liver dysfunction, which has caused it to be removed from the market in Canada and many European countries, although it remains available in the United States. Because of this potential risk, tolcapone should be the second choice of COMT inhibitors, and Entacapone (Comtan) generally the first choice, even though tolcapone is a more potent inhibitor of COMT than entacapone.