It’s reported that iNKT cells are implicated in sickle cell disease (SCD), being both increased and activated in patients compared to controls. But iNKT cell depletion or activation blockage in an SCD mouse model led to reduced pulmonary inflammation and injury. Generally, one strategy employed to decrease iNKT cell activation in these mice involved treatment with a selective adenosine A2A receptor (A2AR) agonist. Besides, studies have demonstrated that A2AR agonists can alleviate hypoxia-induced tissue inflammation in SCD mice. In addition, the primary mediator of the A2AR agonist’s anti-inflammatory effects happens to be the minor lymphocyte subset, invariant natural killer T (iNKT) cells. Regadenoson, a selective A2A adenosine receptor agonist and coronary vasodilator, received FDA approval in April 2008.

Regadenoson is a selective A2A adenosine receptor agonist for inflammation research.

In primary mouse brain endothelial cells, Regadenoson (1 μΜ, 72 h) effectively reduces P-gp expression and functionality in vitro. Moreover, his regulatory process initiated by Regadenoson involves MMP9 activation, ubiquitination, and subsequent translocation to the cytoskeletal fraction. Therefore, the resulting modulation provides an adaptable therapeutic window that enables precise adjustments for improved drug transport to the brain. As a result, this approach holds significant promise as a central nervous system (CNS) drug-delivery technology, showcasing potential advancements in targeted neuropharmacological treatments.

Regadenoson, when administered in awake dogs in varying doses (0.1-5 μg/kg; p.i.v.; single), enhances coronary blood flow (CBF) while reducing mean coronary resistance in a dose-dependent fashion. Specifically, at 2.5 μg/kg, Regadenoson rapidly bolsters coronary blood flow in these animals. Moreover, in rats, Regadenoson (0.5 μg/kg; i.v.; single) enhances Temozolomide delivery to the central nervous system (CNS) when given either 60 or 90 minutes after Temozolomide administration.

In summary, Regadenoson is a selective A2A adenosine receptor agonist and coronary vasodilator, and is a potential anti-inflammation agent.

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[4] Kim DG, et al. J Clin Invest. 2016 May 2;126(5):1717-33.