Istradefylline
Adenosine A2A receptor antagonists
Adenosine A2A receptor antagonists
Oral adenosine A2A receptor blocker added to levodopa to shorten «off» episodes in Parkinson disease.
Quick facts
- Group
- Adenosine A2A receptor antagonists
- Target
- Adenosine A2A receptor
- Used for
- Adjunct to levodopa
- Key effects
- Dyskinesia · Dizziness · Nausea
- Monitor
- Frequency and length of «off» periods · Dyskinesia
- ATC
- N04CX01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows istradefylline bound to the human adenosine A2A receptor.
Istradefylline is an antagonist of the adenosine A2A receptor. In the striatum these receptors are co-located with dopamine D2 receptors, and adenosine acting on them inhibits D2 signalling. By blocking A2A, istradefylline releases that inhibition and lets the remaining dopamine (and levodopa-derived dopamine) act more effectively, which reduces «off» time.
- Blocks adenosine A2A receptors on striatal neurons
- Removes the A2A brake on D2 dopamine signalling
- Remaining dopamine works better
- «Off» episodes on levodopa become shorter
Indications
- Adjunct to levodopa with carbidopa for «off» episodes in adults with Parkinson disease Parkinson disease →
Adverse effects
Common
- Dyskinesia (new or worse involuntary movements)
- Dizziness
- Nausea
- Constipation and loss of appetite
- Insomnia
Contraindications
- Hypersensitivity to istradefylline or to any ingredient of the tablet
Key interactions
- St John's wort
- May reduce the effect of istradefylline.
- Tobacco smoking
- May reduce the effectiveness of istradefylline.
- Levodopa
- Intended combination; dyskinesia may increase.
What is monitored
- Frequency and length of «off» periods
- Dyskinesia
- Hallucinations, confusion and psychotic symptoms
- Impulse-control behaviours (ask patient and family)
- Liver disease, which calls for caution
Administration and safety
- Oral tablet taken at about the same time every day.
- Ask about smoking, which can make it less effective.
- Review herbal products, especially St John's wort.
Pregnancy and breastfeeding
Pregnancy is avoided during treatment and effective contraception is advised; a pregnancy is reported to the treating doctor at once.
Nursing care
- Ask about history of psychosis, dyskinesia or liver disease before starting.
- Teach patient and family to report hallucinations, suspicion, aggression or confusion.
- Ask directly about gambling, shopping, eating or sexual urges that are hard to control.
- Record «on» and «off» times to judge benefit.
Pharmacokinetics
- Absorption
- Oral tablet, once daily, with or without food.
- Metabolism
- Smoking and St John's wort can lower its effect.
Test yourself
Think of the answer, then tap the question to see it.
What receptor does istradefylline block?
The adenosine A2A receptor in the striatum.
For what problem in Parkinson disease is istradefylline added?
«Off» episodes in patients taking levodopa with carbidopa.
Which two serious psychiatric or behavioural effects can istradefylline cause?
Hallucinations or other psychotic symptoms, and impulse-control problems such as compulsive gambling.
Connections
← Back to the class: Adenosine A2A receptor antagonists
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 (MedlinePlus (U.S. National Library of Medicine), 2019); RCSB PDB - 8RW0: Crystal structure of the adenosine A2A receptor in complex with Istradefylline (RCSB Protein Data Bank, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.