ADORA2A and Parkinson disease: Adenosine binds to its inhibitory A1Rs (coupled to Gαi) and its excitatory A2A receptors (A2AR, coupled to Gαs), and A2ARs are believed to contribute to the pathogenesis of PD, which has prompted the development of small molecular agents for potential PD therapy, including apedenoson, preladenant, regadenoson and SYN-115 [24, 63].