catechol-o-methyltransferase inhibitor catechol-o-methyltransferase inhibitor a catechol-o-methyltransferase (comt) inhibitor is a drug that inhibits the enzyme catechol-o-methyltransferase. this enzyme methylates catecholamines such as dopamine, norepinephrine and epinephrine. it also methylates levodopa. comt inhibitors are indicated for the treatment of parkinson's disease in combination with levodopa and an aromatic l-amino acid decarboxylase inhibitor (e.g. carbidopa or benserazide). the therapeutic benefit of using a comt inhibitor is based on its ability to prevent the methylation of levodopa to 3-o-methyldopa, thus increasing the bioavailability of levodopa. comt inhibitors significantly decrease off time in people with parkinson's disease also taking carbidopa/levodopa. metabolism of levodopa by catechol-o-methyltransferase (comt) and aromatic l-amino acid decarboxylase (aadc). comt inhibitors prevent the conversion of levodopa to 3-o-methyldopa. list of comt inhibitors entacapone (comtan, comtess, stalevo) nebicapone nitecapone opicapone (ongentys) tolcapone (tasmar) entacapone and opicapone are peripheral inhibitors, unable to cross the blood-brain barrier. tolcapone is able to cross the blood-brain barrier. tolcapone has been associated with at least three fatal cases of acute liver failure and is thus only rarely prescribed. patients taking tolcapone must be monitored for hepatic failure. entacapone and opicapone have not been associated with hepatotoxicity. adverse effects nausea orthostatic hypotension vivid dreams confusion hallucinations hepatotoxicity (only tolcapone) diarrhea drowsiness urine discoloration dyskinesia