[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/) › Opicapone

# Opicapone

## COMT inhibitors?

COMT inhibitors

Once-daily peripheral COMT inhibitor added to levodopa with carbidopa to treat end-of-dose «wearing-off» in Parkinson disease.

Updated Nov 1, 2026

## Quick facts

**Group**
[COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)

**Target**
Catechol-O-methyltransferase (COMT)

**Used for**
Adjunct to levodopa

**Key effects**
Dyskinesia · Constipation and dry mouth · Insomnia

**Monitor**
«On» and «off» time and dyskinesia · Hallucinations

**ATC**
N04BX04

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**Catechol-O-methyltransferase (COMT)**Opicapone

ⓘ The figure shows opicapone bound to rat COMT with S-adenosylhomocysteine and magnesium; the catechol site is the same in the human enzyme.

**Target in 3D:** Catechol-O-methyltransferase (COMT). PDB structure 7XGI (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7XGI) · Drag to rotate · pinch to zoom

When carbidopa blocks peripheral DOPA decarboxylase, COMT becomes the main enzyme that degrades levodopa outside the brain, to 3-O-methyldopa. Opicapone inhibits peripheral COMT, so more levodopa reaches the brain and each dose lasts longer. Although its plasma half-life is short, it leaves the enzyme very slowly, which allows a single daily dose.

- Inhibits COMT in peripheral tissues
- Less levodopa is converted to 3-O-methyldopa
- More levodopa reaches the brain for longer
- «On» time is extended and wearing-off is reduced

## Indications

- Adjunct to levodopa with carbidopa for end-of-dose «wearing-off» in Parkinson disease [Parkinson disease →](https://durgical.com/en/conditions/parkinson-disease/)

## Adverse effects

### Common

- Dyskinesia
- Constipation and dry mouth
- Insomnia
- Dizziness and orthostatic hypotension
- Weight loss

### Serious (rare, important)

- Hallucinations, delusions and aggressive behaviour
- Sudden sleep during daily activities
- Impulse-control problems
- Fainting
- Fever, rigidity and confusion if it is stopped abruptly

## Contraindications

- Use with non-selective MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid), or within two weeks of stopping them
- Pheochromocytoma or paraganglioma

## Key interactions

**Non-selective MAO inhibitors**
Combined block of both catecholamine-degrading enzymes; the combination is avoided.

**Alcohol**
Adds to the drowsiness.

**Levodopa**
Intended potentiation; dyskinesia may increase and the levodopa dose may need adjusting.

## What is monitored

- «On» and «off» time and dyskinesia
- Blood pressure lying and standing
- Daytime sleepiness and sudden sleep episodes
- Hallucinations and impulse-control behaviours

## Administration and safety

- Oral capsule, usually once a day at bedtime, at least an hour before or after eating.
- It is not stopped suddenly; withdrawal is gradual.
- The surgical or dental team is told the patient takes it.

## Pregnancy and breastfeeding

Information is limited; a pregnancy during treatment is reported to the treating doctor.

## Nursing care

- Ask about MAO inhibitors and about pheochromocytoma before starting.
- Teach to rise slowly from bed and to report fainting.
- Warn about sudden sleep and avoid driving until the effect is known.
- Ask patient and family about hallucinations and compulsive behaviours.

## Pharmacokinetics

**Absorption**
Oral capsule, once daily at bedtime, away from meals.

**Half-life**
Short in plasma, but its tight, slowly reversible binding to COMT keeps the enzyme inhibited through the day.

## Memory aid

OPIcapone: «Once Per night, Inhibits COMT». A bedtime partner that keeps levodopa alive longer.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does opicapone prolong the effect of levodopa?

It inhibits peripheral COMT, so less levodopa becomes 3-O-methyldopa and more reaches the brain.

## How can opicapone be given once daily despite a short plasma half-life?

It dissociates very slowly from COMT, so inhibition lasts long after plasma levels fall.

## Which two conditions or drugs rule out opicapone?

Non-selective MAO inhibitors and pheochromocytoma or paraganglioma.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/opicapone/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 3

- [Entacapone](https://durgical.com/en/pharmacology/entacapone/)
- [Tolcapone](https://durgical.com/en/pharmacology/tolcapone/)
- [Levodopa + carbidopa](https://durgical.com/en/pharmacology/levodopa-carbidopa/)

## Related conditions 1

- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)

[← Back to the class: COMT inhibitors](https://durgical.com/en/pharmacology/classes/comt-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Opicapone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a620059.html) (MedlinePlus (U.S. National Library of Medicine), 2020); [RCSB PDB - 7XGI: COMT SAH Mg opicapone complex](https://www.rcsb.org/structure/7XGI) (RCSB Protein Data Bank, 2023); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N04BX04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/opicapone/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/opicapone/