Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development

March 2019 in “ Frontiers in Cellular Neuroscience ”

Kenneth A. Jacobson, Dilip K. Tosh, Shanu Jain, Zhan‐Guo Gao

adenosine adenosine receptor agonists positive allosteric modulators A₁ receptor A₂A receptor A₂B receptor A₃ receptor Regadenoson AR agonists PAMs

TLDR The document concludes that adenosine receptor agonists have potential for treating various conditions, but only a few are approved due to challenges like side effects and the need for selective activation.

The document reviews the development of adenosine receptor (AR) agonists and positive allosteric modulators (PAMs), highlighting their therapeutic potential in various conditions such as inflammation, pain, cancer, cardiovascular diseases, and metabolic disorders. It discusses the four AR subtypes (A₁, A₂A, A₂B, A₃) and their physiological roles, including energy balance during stress. Despite thousands of AR modulators being reported, only adenosine and Regadenoson are approved for human use, with new compounds showing promise in preclinical and clinical evaluations. The review also addresses the challenges in AR agonist development, such as receptor desensitization and the need for selective activation of specific AR subtypes. It mentions the use of adenosine for promoting hair growth and skin health, and the potential of AR agonists in treating various diseases, with some compounds discontinued due to side effects or lack of efficacy. The document does not specify the number of people involved in the clinical trials mentioned.

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