The future of pharmacologic stress: selective a2a adenosine receptor agonists
Section snippets
Ideal features of a novel pharmacologic stress agent
In SPECT myocardial perfusion imaging, the established pharmacologic stress agents adenosine and dipyridamole provide reproducible coronary vasodilation and significant clinical utility. However, as nonselective adenosine agonists, they are associated with a high incidence of side effects, are contraindicated in bronchospastic disease and high-grade AV nodal block, and require a controlled infusion. In theory, an ideal pharmacologic stress agent would be a selective A2A adenosine receptor
Selectivity, affinity, and clinical implications
The potency of an A2A agonist to induce coronary vasodilation depends primarily on 4 factors: (1) the affinity of the agonist for the target receptor (ie, agonist binding), (2) the density of the receptors at the targeted location, (3) the intrinsic efficacy of the bound agonist to activate the target receptor, and (4) the efficiency of receptor coupling to achieve a full functional response.1
In evaluating the selectivity, affinity, and duration of action of A2A agonists including regadenoson,
Clinical studies of regadenoson
In experimental studies, the A2A adenosine receptor agonist regadenoson has been shown to be a potent and selective coronary vasodilator and holds tremendous promise for use as a pharmacologic stress agent in myocardial perfusion imaging. Preclinical results demonstrate that regadenoson is a 10-fold more potent coronary vasodilator than adenosine (6 nmol/L versus 60 nmol/L, respectively).4 Regadenoson is functionally selective for the A2A adenosine receptor, with no AV block or
Regadenoson, binodenoson, and adenosine
Based on preclinical and early clinical studies reported in the literature, regadenoson is certainly promising as a pharmacologic stress agent. At the 400-μg dose using a rapid (≤10-second) bolus delivery, regadenoson produces a magnitude of maximal hyperemia comparable to adenosine that is rapid in onset (30 seconds) and short in duration (2.8 minutes),10 providing a favorable time frame to facilitate radionuclide imaging. In comparison, maximal hyperemia induced by binodenoson has been
Conclusion
Based on available results from experimental and clinical trials of selective A2A receptor agonists, regadenoson holds significant potential as a pharmacologic stress agent. As a highly selective, potent, low-affinity A2A adenosine agonist, regadenoson produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for myocardial perfusion SPECT imaging. Regadenoson's simple rapid-bolus administration and short duration of hyperemic effect points to an advantage of
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