Background: Adenosine is an endogenous purine nucleoside, which mediates a
variety of important biological processes and diseases, such as vasodilation, inflammation,
cancer, wound healing, ischemia reperfusion injury, Parkinson disease, infectious diseases,
and other CNS disorders. Particularly important are the A2A receptors that have been expressed
in the lung, liver, heart, cardiovascular tissues, leukocytes, neutrophils, and endothelial
cells. This review provides an update of the latest A2A receptor agonists developed in the
period 2005-2017, their selectivity regarding other adenosine receptors and their potential
Methods: I have conducted an extensive search from the most common bibliographic databases
for critically review the most recent works on the A2A receptor agonists and their therapeutic
applications in inflammation, asthma and chronic obstructive pulmonary disease, myocardial
perfusion imaging, sepsis, rheumatoid arthritis, and wound healing, among others.
Results: In the last decade, a great deal of effort has been devoted to develop adenosine receptor
agonists and antagonists for treatment of a number of diseases. Thus, for A2A receptor
agonists more than 130 papers and reviews have been found, many of them highlighting the
usefulness of these compounds in the field.
Conclusions: Although so far many of the A2A receptor agonists have failed in clinical trials
due to their side effects, some of them have been approved for protection against cardiac
ischemia-reperfusion injury and anemia. The recently reported crystal structure of the human
A2A receptor in complex with the agonist UK-432097 is a fundamental keystone for the development
of new and selective A2A ligands with new therapeutic applications.