Abstract
The therapeutic potential of targeting adenosine A(2A) receptors (A(2A)Rs) is immense due to their broad expression in the body and central nervous system. The role of A(2A)Rs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous system functions has been extensively studied. Numerous A(2A)R agonist and antagonist molecules are reported, many of which are currently in clinical trials or have already been approved for treatment. Allosteric modulators can selectively elicit a physiologic response only where and when the orthosteric ligand is released, which reduces the risk of an adverse effect resulting from A(2A)R activation. Thus, these allosteric modulators have a potential therapeutic advantage over classical agonist and antagonist molecules. This review focuses on the recent developments regarding allosteric A(2A)R modulation, which is a promising area for future pharmaceutical research because the list of existing allosteric A(2A)R modulators and their physiologic effects is still short.