Istradefylline: First Global Approval

  title={Istradefylline: First Global Approval},
  author={Rosselle T. Dungo and Emma Deeks},
Kyowa Hakko Kirin is developing istradefylline, a selective adenosine A2A receptor antagonist, for the once-daily oral treatment of Parkinson’s disease (PD). Adenosine A2A receptors are considered to be present particularly in the basal ganglia of the brain; the degeneration or abnormality observed in PD is believed to occur in the basal ganglia, which is recognized to play a significant role in motor control. Commercially available dopamine replacement therapies effectively treat the early… 
The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease
Istradefylline is the first non-dopaminergic drug approved by FDA for PD in the last two decades and paves the way to foster entirely novel therapeutic opportunities for adenosine A2A receptor antagonists, such as neuroprotection or reversal of mood and cognitive deficits in PD and other neuropsychiatric diseases.
The efficacy of oral adenosine A2A antagonist istradefylline for the treatment of moderate to severe Parkinson’s disease
The moderate and severe stages of Parkinson’s disease (PD) are marked by motor and non-motor complications that still remain difficult to control with the currently available therapy. Adenosine A2A
Adenosine A2A Receptor Antagonists in Drug Development
Dual- and multi-target drugs combining A2A antagonism with A1 antagonism, MAO-B inhibition, dopamine receptor activation and/or NMDA receptor blockade may be advantageous for the treatment of PD and perhaps also for other brain diseases.
Adenosine A2A Receptor Antagonists in Parkinson’s Disease: Progress in Clinical Trials from the Newly Approved Istradefylline to Drugs in Early Development and Those Already Discontinued
  • A. Pinna
  • Biology, Psychology
    CNS Drugs
  • 2014
Pharmacological and clinical data available on istradefylline, tozadenant, PBF-509, ST1535, ST4206, V81444, preladenant and vipadenant are summarized, suggesting that A2A antagonists might also be efficacious as monotherapy in patients at an early stage of PD.
Two new adenosine receptor antagonists for the treatment of Parkinson's disease: istradefylline versus tozadenant
Both drugs show promising efficacy for the reduction of OFF time in levodopa-treated Parkinson's disease patients, but further research is needed in order to obtain definitive conclusions.
Istradefylline to Treat Patients with Parkinson’s Disease Experiencing “Off” Episodes: A Comprehensive Review
Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing “off episodes” of Parkinson’s disease.
Efficacy of Adenosine A2A Receptor Antagonist Istradefylline as Augmentation for Parkinson’s Disease: A Meta-analysis of Randomized Controlled Trials
Istradefylline could be an efficacy and safety augmentation drug added on to levodopa or other existing anti-Parkinsonian therapies, limited by the number of studies, future large-scale studies are needed to verify these results.
Emerging Nondopaminergic Medications for Parkinson’s Disease: Focusing on A2A Receptor Antagonists and GLP1 Receptor Agonists
Findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management are summarized and the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors are explained.
Adenosine A2A receptor antagonist istradefylline 20 versus 40 mg/day as augmentation for Parkinson’s disease: a meta-analysis
Results indicate that istradefylline 40 mg/day as augmentation shows potential promise on clinical applicability, and is worthy of further study.
Xanthine derivatives as agents affecting non-dopaminergic neuroprotection in Parkinson`s disease.
The current review summarizes frequently suspected non-dopaminergic neuroprotective mechanisms and the possible beneficial effects of the xanthine derivatives in PD, along with some synthetic approaches to produce perspective xAnthine derivatives as non-Dopamin allergic agents in PD treatment.


Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson’s disease
  • P. Jenner
  • Psychology, Biology
    Expert opinion on investigational drugs
  • 2005
Istradefylline is a novel adenosine A2A receptor antagonist currently in Phase III clinical trials for efficacy in patients with PD and results from Phase II clinical trials demonstrated that it provides a clinically meaningful reduction in ‘off’ time and an increased ‘on” time with non-troublesome dyskinesia in levodopa-treated patients with established motor complications.
Randomized trial of the adenosine A2A receptor antagonist istradefylline in advanced PD
Istradefylline was generally well tolerated and reduced “off” time as assessed by home diaries, and nausea was the most common adverse event.
Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial.
Adenosine A2A receptors and Parkinson's disease.
In clinical trials, the A(2A)AR antagonist istradefylline reduces "off" time in patients with PD receiving optimal dopaminergic therapy, however, these effects have proven difficult to demonstrate on a consistent basis, and further clinical trials are required to establish the clinical utility of this drug class.
Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations
It is concluded that istradefylline is well tolerated and significantly reduces OFF time as an adjunct to levodopa in PD subjects with motor fluctuations.
Adenosine A(2A) receptor antagonist treatment of Parkinson's disease.
The hypothesis that A(2A) receptor mechanisms contribute to symptom production in PD and that drugs able to selectively block these receptors may help palliate symptoms in levodopa-treated patients with this disorder is supported.
Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys
Adenosine A2A receptor antagonists have antiparkinsonian effects of their own with a reduced propensity to elicit dyskinesias and might therefore be useful agents in the treatment of PD.
Adenosine A2A Antagonist: A novel antiparkinsonian agent that does not provoke dyskinesia in Parkinsonian monkeys
The results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.
A long-term study of istradefylline in subjects with fluctuating Parkinson's disease.