Allosteric Modulation of Adenosine A 2A Receptors as a New Therapeutic Avenue.

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.