Istradefylline
FDA-approved adenosine A2A antagonist for OFF episodes in Parkinson's disease, with a non-dopaminergic mechanism.
Pharmacology
Contents
WHAT IS ISTRADEFYLLINE?
Detailed overview
Istradefylline (KW-6002, brand name Nourianz) is a selective adenosine A2A receptor antagonist approved by the FDA in 2019 as an add-on to levodopa/carbidopa for reducing so-called OFF episodes in Parkinson's disease. It blocks A2A receptors in the striatum, counteracting adenosine's inhibitory effect on the dopaminergic motor pathway without directly stimulating dopamine receptors. This non-dopaminergic target distinguishes it from conventional dopaminergic drugs. It is dosed once daily in the morning because its half-life is long (~80 hours), and multiple randomized clinical trials have shown it reduces daily OFF time compared with placebo.
Mechanism
Selective adenosine A2A antagonist
Half-life
~80 hours (once daily, morning)
Legal status
FDA-approved prescription drug (2019)
Receptor profile
- Adenosine A2A receptorStrong
- Striatal dopamine D2 pathway (indirect)Moderate
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Worsening of dyskinesia (involuntary movements), especially when combined with levodopa
- Dizziness, headache
- Nausea and constipation
- Insomnia (hence morning dosing is advised)
- Hallucinations and other psychiatric symptoms, mainly in elderly or susceptible patients
- Impulse-control disorders (e.g. gambling) rarely, as with dopaminergic treatments in general
Contraindications · 5
- Pregnancy: showed developmental toxicity in animal studies, avoid
- Severe hepatic impairment (Child-Pugh C): not recommended because clearance is reduced
- History of psychosis or hallucinations: symptoms may worsen
- Concomitant strong CYP3A4 inhibitors (dose must be halved) and strong CYP3A4 inducers should be avoided
- Heavy smoking (over 20 cigarettes/day) markedly lowers blood levels; a higher dose may be needed
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005)
Hauser RA, Shulman LM, Trugman JM, et al.
Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations
Stacy M, Silver D, Mendis T, et al.
Clinical efficacy of istradefylline (KW-6002) in Parkinson's disease: a randomized, controlled study
Mizuno Y, Hasegawa K, Kondo T, et al.
Adenosine A2A receptor antagonist istradefylline reduces daily OFF time in Parkinson's disease
Pourcher E, Fernandez HH, Stacy M, et al.
A long-term study of istradefylline safety and efficacy in patients with Parkinson disease
Factor SA, Wolski K, Togasaki DM, et al.
Efficacy and safety of istradefylline for Parkinson's disease: A systematic review and meta-analysis
Jing XZ, Yang JR, Wang XX, et al.
FAQ
FAQ
FDA-approved adenosine A2A antagonist for OFF episodes in Parkinson's disease, with a non-dopaminergic mechanism.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.