Pharmacology · Class
COMT inhibitors !
Add-on drugs that make each levodopa dose last longer by blocking its breakdown by COMT. Used for end-of-dose «wearing-off».
Updated 2026-11-01
What they are
Entacapone, tolcapone and opicapone inhibit catechol-O-methyltransferase. They have no antiparkinson effect on their own and are always given with levodopa plus a decarboxylase inhibitor.
Mechanism of action
When DOPA decarboxylase is blocked by carbidopa, COMT becomes the main enzyme that destroys levodopa (to 3-O-methyldopa). Blocking COMT keeps levodopa levels up for longer, so «on» time lasts longer.
Target: Catechol-O-methyltransferase (COMT)
Drugs in this class
- EntacaponeA COMT inhibitor given with every levodopa + carbidopa dose to make it last longer. Colours urine brownish-orange.Catechol-O-methyltransferase (COMT)
- TolcaponeA COMT inhibitor that extends levodopa, reserved for selected patients because it can cause fatal liver failure.Catechol-O-methyltransferase (COMT)
Others in the class
- Opicapona
Test yourself
Think of the answer, then tap the question to see it.
Why are COMT inhibitors useless without levodopa?
They do not stimulate dopamine receptors; they only slow the breakdown of levodopa.
Which COMT inhibitor carries a boxed warning for liver failure?
Tolcapone.
Which motor problem are COMT inhibitors used for?
End-of-dose «wearing-off» in patients on levodopa.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023); DailyMed - ENTACAPONE tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - TOLCAPONE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.