There is an increase in the therapeutic index and locomotor improvement of L-DOPA with adenosine A2AR antagonists, like istradefylline (25, 132) and tozadenant (26), and/or D2R agonists, based on the existence of A2A–D2R heteromers (24, 133), which function also as a biomarker to monitor PD (134). This evidence concerns the gene DRD2 and Parkinson disease.