Adenosine produces coronary vasodilation through activation of A-2a adenosine receptors. However adenosine also acts at Al adenosine receptors to slow atrioventricular conduction and when injected into man induces chest pain that can be blocked with Al receptor antagonists. DTI has synthesized a number of adenosine analogs that activate only the A2a subtype of adenosine receptor and have identified WRC-0470 as a potent selective short acting coronary vasodilator. It is our belief that WRC- 0470 will prove to be superior to currently available pharmacological stress agents and will therefore be a useful diagnostic aid in myocardial imaging techniques. We willi) develop synthetic chemical procedures for the efficient scale up of bulk material,ii) determine the stability of the compound in a variety of solutions and identify a suitable vehicle for use as an injectable drug, iii) determine the safety and the optimal mode of administration of the drug in a conscious dog model in which coronary vasodilation and other cardiovascular parameters may be measured simultaneously.Phase II will support manufacture of clinical trials supplies, toxicology, and Phase I and Phase II clinical trials.National Heart, Lung, and Blood Institute (NHLBI)
