ADORA2A and drug-induced dyskinesia: While some clinical trials failed to demonstrate a large benefit of A2AR blockade as monotherapy in PD patients even reducing off-time (SYN-115; Hauser et al., 2014), the A2AR antagonist istradefylline (KW-6002) is still tested in phase III and it is already approved as therapeutic option for PD patients in Japan where it is early administered in association with L-DOPA to reduce motor symptoms and dyskinesia (Borea et al., 2016; Oertel and Schulz, 2016).