Emerging adenosine receptor agonists

Adenosine receptors (ARs) are a four-member subfamily of G protein-coupled receptors and are major targets of caffeine and theophylline. There are four subtypes of ARs, designated as A(1), A(2A), A(2B) and A(3). Selective agonists are now available for all four subtypes. Over a dozen of these selective agonists are now in clinical trials for various conditions, although none has received regulatory approval except for the endogenous AR agonist adenosine itself. A(1)AR agonists are in clinical trials for cardiac arrhythmias and neuropathic pain. A(2A)AR agonists are now in trials for myocardial perfusion imaging and as anti-inflammatory agents. A(2B)AR agonists are under preclinical scrutiny for potential treatment of cardiac ischemia. A(3)AR agonists are in clinical trials for the treatment of rheumatoid arthritis and colorectal cancer. The present review will mainly cover the agonists that are presently in clinical trials for various conditions and only a brief introduction will be given to major chemical classes of AR agonists presently under investigation.