[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Adenosine A2A receptor antagonists](https://durgical.com/en/pharmacology/classes/adenosine-a2a-receptor-antagonists/) › Istradefylline # Istradefylline ## Adenosine A2A receptor antagonists? Adenosine A2A receptor antagonists Oral adenosine A2A receptor blocker added to levodopa to shorten «off» episodes in Parkinson disease. Updated Nov 1, 2026 ## Quick facts **Group** [Adenosine A2A receptor antagonists](https://durgical.com/en/pharmacology/classes/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. 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 ◎**Adenosine A2A receptor**Istradefylline ⓘ The figure shows istradefylline bound to the human adenosine A2A receptor. **Target in 3D:** Adenosine A2A receptor. PDB structure 8RW0 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/8RW0) · Drag to rotate · pinch to zoom 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 →](https://durgical.com/en/conditions/parkinson-disease/) ## Adverse effects ### Common - Dyskinesia (new or worse involuntary movements) - Dizziness - Nausea - Constipation and loss of appetite - Insomnia ### Serious (rare, important) - Hallucinations, paranoid ideas, delusions, agitation or confusion - Impulse-control problems: gambling, hypersexuality, compulsive spending or eating ## 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. ## Memory aid IstrADEfylline: blocks ADEnosine A2A so dopamine D2 gets the green light; levodopa partner, never solo. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/istradefylline/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Connections ## Related drugs 2 - [Levodopa + carbidopa](https://durgical.com/en/pharmacology/levodopa-carbidopa/) - [Opicapone](https://durgical.com/en/pharmacology/opicapone/) ## Related conditions 1 - [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/) [← Back to the class: Adenosine A2A receptor antagonists](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a619053.html) (MedlinePlus (U.S. National Library of Medicine), 2019); [RCSB PDB - 8RW0: Crystal structure of the adenosine A2A receptor in complex with Istradefylline](https://www.rcsb.org/structure/8RW0) (RCSB Protein Data Bank, 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N04CX01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/istradefylline/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/istradefylline/