Adenosine receptors pharmacology and rapiscan

Adenosine receptors occur throughout the body.  Adenosine is a nucleoside and is known to act as an autocoid – that is, a small molecule hormone that acts upon the very same cells that produce it. ^1,2

Adenosine is produced locally under conditions of uncommon stress and has been referred to as the retaliatory metabolite. ^1,2

In the heart, the A_2A adenosine receptor is responsible for coronary vasodilation resulting in an increase in coronary blood flow and is believed to cause sympathoexcitation, wheras the A₁ receptor slows arterioventricular (AV) and sinoatrial (SA) nodal conduction.^2-5

In the lung, the A_2B and A₃ adenosine receptors have been implicated in the pathophysiology of bronchoconstriction in susceptible individuals (i.e., asthmatics).²

Regadenoson is a low affinity agonist (Ki ≈ 1.3 μM) for the A_2A adenosine receptor, with at least 10-fold lower affinity for the A₁ adenosine receptor, and very low, if any, affinity for the A_2B and A₃ adenosine receptors.⁶

Despite low affinity for the A_2A adenosine receptor, in animal models, regadenoson has high potency for increasing coronary conductance (an indirect measure of coronary blood flow velocity) and selectivity (≥ 215-fold) for increasing coronary conductance (A_2A-mediated response) relative to slowing of cardiac AV nodal conduction (A₁-mediated response) as measured by AV conduction time.⁶

Due to differences in receptor density and the selectivity of Rapiscan, in animals regadenoson was shown to preferentially increase blood flow in coronary relative to peripheral (forelimb, brain, pulmonary) arterial vascular beds.^6,7

In a human clinical trial, Rapiscan was shown to cause a rapid increase in blood flow, which is sustained for several minutes - sufficient for radionuclide myocardial extraction.^6,8