Istradefylline - a First Generation Adenosine A Antagonist for the Treatment of Parkinson's Disease

It is now accepted that Parkinson's disease (PD) is not simply due to dopaminergic dysfunction, and there is interest in developing non-dopaminergic approaches to disease management. Adenosine A receptor antagonists represent a new way forward in the symptomatic treatment of PD. In this narrative review, we summarize the literature supporting the utility of adenosine A antagonists in PD with a specific focus on istradefylline, the most studied and only adenosine A antagonist currently in clinical use.: At this time, the use of istradefylline in the treatment of PD is limited to the management of motor fluctuations as supported by the results of randomized clinical trials and evaluation by Japanese and USA regulatory authorities. The relatively complicated clinical development of istradefylline was based on classically designed studies conducted in PD patients with motor fluctuations on an optimized regimen of levodopa plus adjunctive dopaminergic medications. In animal models, there is consensus that a more robust effect of istradefylline in improving motor function is produced when combined with low or threshold doses of levodopa rather than with high doses that produce maximal dopaminergic improvement. Exploration of istradefylline as a 'levodopa sparing' strategy in earlier PD would seem warranted.