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# Adenosine A2A receptor antagonists

Non-dopaminergic add-on for Parkinson disease: blocking striatal A2A receptors boosts D2 signalling and shortens «off» time on levodopa.

Updated Nov 1, 2026

## What they are

Istradefylline is the member in clinical use. It is added to levodopa (with a decarboxylase inhibitor) for «off» episodes in Parkinson disease. It is not a dopamine agonist and does not act on dopamine metabolism.

## Mechanism of action

In the striatum, A2A adenosine receptors sit next to D2 dopamine receptors on the same neurons, and adenosine acting on A2A dampens D2 signalling, possibly through A2A–D2 heteromers. Blocking A2A removes that brake, so the dopamine left in the Parkinsonian striatum works better and movement improves.

Target: Adenosine A2A receptor (striatum)

## Key points

- Add-on to levodopa for «off» episodes; not used alone.
- Main adverse effects: dyskinesia, hallucinations, nausea, dizziness, insomnia.
- Smoking can lower its effect; St John's wort interacts.
- Impulse-control behaviours have been reported, as with other antiparkinson drugs.

## Drugs in this class

- [**Istradefylline** Oral adenosine A2A receptor blocker added to levodopa to shorten «off» episodes in Parkinson disease. Adenosine A2A receptor](https://durgical.com/en/pharmacology/istradefylline/)

## Test yourself

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

## How does blocking A2A receptors improve parkinsonism?

Striatal A2A receptors inhibit D2 signalling; blocking them strengthens the effect of the remaining dopamine.

## Is istradefylline used as monotherapy?

No: it is an add-on to levodopa for «off» episodes.

## Which habit can reduce the effect of istradefylline?

Smoking tobacco.

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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: [Istradefylline: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a619053.html) (MedlinePlus (U.S. National Library of Medicine), 2019); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N04CX01) (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/adenosine-a2a-receptor-antagonists/