Recent progress in the discovery of adenosine A(2A) receptor antagonists for the treatment of Parkinson's disease.

Antagonism of the adenosine A2A receptor has emerged as a promising non-dopaminergic approach for the potential treatment of Parkinson's disease (PD). Several pharmaceutical and academic institutions have ongoing research programs in this area, and orally efficacious A2A receptor antagonists have been advanced into clinical development. Traditionally, antagonists of the A2A receptor are classified as xanthine and non-xanthine derivatives. This review provides a detailed summary of the recent SAR development that has led to the discovery of promising non-xanthine-based A2A receptor antagonists. The current clinical status and the potential utility of A2A receptor antagonists in indications other than PD are also discussed.