Allosteric Modulation of Adenosine A2A Receptors as a New Therapeutic Avenue

Abstract

The therapeutic potential of targeting adenosine A2A receptors (A2A Rs) is immense due to their broad expression in the body and central nervous system. The role of A2A Rs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous system functions has been extensively studied. Numerous A2A 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 A2A 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 A2A R modulation, which is a promising area for future pharmaceutical research because the list of existing allosteric A2A R modulators and their physiologic effects is still short.