COMT

Class

inhibitor

Catechol-O-methyltransferase (COMT) is an enzyme that breaks down catecholamines, a family of molecules that includes dopamine, norepinephrine, and the drug levodopa, by adding a methyl group to them. COMT acts throughout the body, including the intestine, liver, and bloodstream, but this mechanism is most relevant in the treatment of Parkinson's disease. Levodopa is given to replenish dopamine in the brain, but a large fraction of an oral dose is metabolized before it ever reaches the brain, both by an enzyme called aromatic amino acid decarboxylase and by COMT. Levodopa is typically co-administered with a decarboxylase inhibitor to block one route, but COMT remains active and continues to degrade levodopa, shortening how long each dose remains effective. Inhibiting COMT reduces this peripheral breakdown, extending the amount of levodopa available to cross into the brain and be converted to dopamine. This approach does not treat Parkinson's disease directly but improves the pharmacokinetic behavior of levodopa, helping smooth out fluctuations in symptom control that arise as the disease progresses and the therapeutic window narrows. COMT inhibition is a well-established adjunctive strategy in movement disorder pharmacology rather than a standalone therapy.