Novel selective antagonist radioligands for the pharmacological study of A2B adenosine receptors

The adenosine A_2B receptor is the least well characterized of the four adenosine subtypes due to the lack of potent and selective agonists and antagonists. Despite the widespread distribution of A_2B receptor mRNA, little information is available with regard to their function. The characterization of A_2B receptors, through radioligand binding studies, has been performed, until now, by using low-affinity and non-selective antagonists like 1,3-dipropyl-8-cyclopentylxanthine (³H]DPCPX),(4-(2-7-amino-2-(2-furyl)-1,2,4]triazolo-2,3-a]1,3,5]triazin-5-ylamino]ethyl)-phenol (³H]ZM 241385) and 3-(3,4-aminobenzyl)-8-(4-oxyacetate)phenyl-1-propyl-xanthine (¹²⁵I]ABOPX). Recently, high-affinity radioligands for A_2B receptors, N-(4-cyanophenyl)-2-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy]acetamide (³H]MRS 1754), N-(2-(2-Phenyl-6-4-(2,2,3,3-tetratritrio-3-phenylpropyl)-piperazine-1-carbonyl]-7H-pyrrolo2,3-d]pyrimidin-4-ylamino)-ethyl)-acetamide (³H]OSIP339391) and N-benzo1,3]dioxol-5-yl-2-5-(1,3-dipropyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]-acetamide] (³H]MRE 2029F20), have been introduced. This minireview offers an overview of these recently developed radioligands and the most important applications of drugs towards A_2B receptors.