Tolcapone (tradename Tasmar) is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT).

Tolcapone is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication.

Tolcapone is a yellow, odorless, non-hygroscopic, crystalline compound with a relative molecular mass of 273.25. The chemical name of tolcapone is 3,4-dihydroxy-4’-methyl-5-nitrobenzophenone. Its empirical formula is C₁₄H₁₁NO₅.

Tolcapone has the ability to cross the blood–brain barrier and thus exerts its COMT inhibitory effects in the CNS as well as in the periphery.

Tolcapone has demonstrated significant hepatotoxicity that limits the drug's utility. Entacapone, another COMT inhibitor, is an alternative selection for L-DOPA adjunct therapy in the treatment of Parkinson's disease, largely since it has a more favorable toxicity profile.

Normally, administration of levodopa is compromised when COMT converts it to 3-methoxy-dopa. By preventing this effect, more of the levodopa that is administered reaches the CNS. Additionally, levodopa that is in the CNS, after being converted to dopamine, will not be degraded by COMT when tolcapone inhibits COMT activity.