INTRODUCTION: Recent experimental and clinical research has shown that A2A 
adenosine receptor antagonism can bring about an improvement in the motor 
behavior of patients with Parkinson's disease. Istradefylline , a xanthine 
derivative, has the longest half-life of all the currently available A2A 
adenosine receptor antagonists; it can successfully permeate through the 
blood-brain barrier and has a high human A2A adenosine receptor affinity.
AREAS COVERED: In this article, the author discusses the potential role of A2A 
adenosine receptor antagonists in the treatment of Parkinson's disease through 
the evaluation of istradefylline. Specifically, the article reviews the clinical 
and pharmacokinetic information available to elucidate its therapeutic 
potential.
EXPERT OPINION: A2A adenosine receptor antagonists are efficacious in 
combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and 
causes long-term behavioral and metabolic side effects. Future research on A2A 
adenosine receptor antagonism should consider compounds like istradefylline as 
l-dopa and/or dopamine agonist-sparing treatment alternatives, since their 
clinical handling, safety and side-effect profile are superior to l-dopa and/or 
dopamine agonists. The current focus to demonstrate a specific 
dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in 
clinical trials is risky, since the presentation of dyskinesia varies on a 
day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. 
The demonstration of an antidyskinetic effect may convince authorities, but this 
is far less relevant in clinical practice as patients generally better tolerate 
dyskinesia than other phenomena and dopaminergic side effects.