AMP 579, a Novel Adenosine Agonist for the Treatment of Acute Myocardial Infarction

The discovery that the endogenous autocoid adenosine plays a role in the ability of the myocardium to protect itself against ischemia has prompted a significant effort to identify stable cardioprotective adenosine agonists. This review summarizes current data regarding AMP 579, a novel adenosine receptor agonist with high affinity for the A 1 (K i = 2 nM) and A 2A (K i = 56 nM) receptor subtypes. In models of acute myocardial infarction (MI) in rats, pigs, and dogs, AMP 579 is a highly effective cardioprotective agent, when given prior to ischemia reducing infarct size by 63, 98, and 53%, respectively, and significantly reducing the incidence of ventricular fibrillation. Moreover, in rodent and porcine models of acute MI AMP 579 is still able to reduce infarct size by greater than 50% when administered just prior to reperfusion. This cardioprotective profile suggests that intravenous AMP 579 should prove therapeutically valuable when given as an adjunct to revascularization in patients suffering MI or undergoing coronary artery bypass grafting. Importantly, preclinical toxicology studies reveal no cause for concern regarding the potential therapeutic applications of AMP 579, which will entail only an acute intravenous administration. In addition, initial clinical experience with AMP 579 has been positive with an acceptable tolerability and a favorable pharmacokinetic profile, indicating that plasma levels of the drug can be rapidly and predictably controlled. Finally, the positive data from the Acute Myocardial Study of Adenosine (AMISTAD) trial, a small phase II study, indicate adenosine is able to reduce infarct size when given as an adjunct to thrombolysis in patients with anterior MI, raising confidence that the cardioprotective effects of adenosine agonists (e.g., AMP 579) seen in preclinical studies should translate into the clinic. In this regard, AMP 579 is currently undergoing pivotal phase II studies in patients suffering acute MI.