Adenosine A2A agonists in development for the treatment of inflammation.
Extracellular adenosine binds specifically to a family of four G protein-coupled cell-surface adenosine receptors (ARs). As the activation of the A2AAR modulates the activity of multiple inflammatory cells including neutrophils, macrophages and T lymphocytes, the receptor is considered to be a promising pharmacological target for the treatment of inflammatory disorders. Although adenosine binds nonselectively to all four AR subtypes, A2AAR selective agonists have been developed and shown to inhibit multiple manifestations of inflammatory cell activation including superoxide anion generation, cytokine production and adhesion molecule expression. A2AAR agonists are also vasodilators, but the inhibition of inflammation occurs at low doses that produce few or no cardiovascular side effects. Therefore, the selective activation of the A2AAR by these compounds holds significant potential in the treatment of inflammation.
Lappas
Courtney M
CM
Department of Pharmacology, University of Virginia, Box 801394, Charlottesville VA 22908, USA.
Sullivan
Gail W
GW
Linden
Joel
J
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000639:trends*
D058908:Adenosine A2 Receptor Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015507:Drugs, Investigational; D043705:Receptor, Adenosine A2A