To the best of our knowledge, the present study is the first comprehensive demonstration of positive allosteric modulation of the A2aR. Because of its anti-inflammatory and immunomodulatory role, the A2aR has been a therapeutic target for a number of disease conditions characterized by inflammation such as sepsis, ischemia, rheumatoid arthritis, and wound healing [25,29]. This evidence concerns the gene ADORA2A and rheumatoid arthritis.