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[Pharmacology](https://durgical.com/en/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)

## Key points

- They boost levodopa, so dyskinesias, nausea and hallucinations can increase; the levodopa dose is often lowered.
- Tolcapone can cause fatal fulminant liver failure: reserved for patients not helped by other options, with liver tests.
- Entacapone acts mainly outside the brain and has not been linked to liver toxicity; it turns urine brownish-orange.
- Diarrhoea is common; they are avoided with nonselective MAO inhibitors.

## Drugs in this class

- [**Entacapone** A COMT inhibitor given with every levodopa + carbidopa dose to make it last longer. Colours urine brownish-orange. Catechol-O-methyltransferase (COMT)](https://durgical.com/en/pharmacology/entacapone/)
- [**Tolcapone** A COMT inhibitor that extends levodopa, reserved for selected patients because it can cause fatal liver failure. Catechol-O-methyltransferase (COMT)](https://durgical.com/en/pharmacology/tolcapone/)

## 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.

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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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=56327e32-3b06-4144-91a0-bb1908842e33) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - TOLCAPONE tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd367eec-359a-4065-b5c3-7c0107c823fe) (DailyMed (U.S. National Library of Medicine), 2021); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N04BX) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/comt-inhibitors/