5-yl-amino]ethyl)phenol, a High Affinity Antagonist Radioligand Selective for the A2a Adenosine Receptor

The A2a adenosine receptor (AR) mediates several important physiological effects of adenosine, including vasodilation and inhibition of platelet aggregation. Until recently, no antagonist radioligand of sufficient selectivity or affinity was available. We describe the synthesis and characterization by radioligand binding of 1251-4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a}-(1,3,5}triazin-5-yI-amino]ethyl)phenol (125l-ZM241385) in mem-branes from two cell types that express A2a ARs. Membranes from Chinese hamster ovary (CHO) cells expressing a recom-binant canine t2a AR bound 125I-ZM241385 with high affinity, and agonist competition experiments with 2-(p-carboxyethyl)-phenylamino-5 ‘-N-carboxamidoadenosine, 5 ’-N-ethylcarbox-amidoadenosine, and (-)-N6-[(R)-phenylisopropyl]adenosine revealed a potency order characteristic of an A2a AR binding site. Membranes from bovine striatum, which contain a nativ