ADORA2A and Parkinson disease: Over 25 clinical trials have been performed to assess the safety profile and clinical effectivity of A2AR antagonists in PD patients, including eight phase IIb and III double-blind, placebo-controlled studies of istradefylline (KW-6002, > 4000 PD patients), one phase IIb trial assessing preladenant (SCH 420814, 253 PD patients), and one phase IIb trial evaluating tozadenant in 337 PD patients.