Emerging adenosine receptor agonists

Abstract

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 A₁, A_2A, A_2B and A₃. 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. A₁AR agonists are in clinical trials for cardiac arrhythmias and neuropathic pain. A_2AAR agonists are now in trials for myocardial perfusion imaging and as anti-inflammatory agents. A_2BAR agonists are under preclinical scrutiny for potential treatment of cardiac ischemia. A₃AR 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.

Keywords::

• adenosine receptor
• agonist
• cardiac arrhythmia
• cardiac perfusion imaging
• colon cancer
• G protein-coupled receptor
• inflammation
• nucleoside
• pain
• rheumatoid arthritis

Acknowledgements

Supported by the National Institute of Health and the National Institute of Diabetes and Digestive and Kidney Intramural Research Program. The authors declare no conflict of interest.

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