Recent advances in adenosine receptor antagonist research

Four types of adenosine receptors (ARs) have been identified and designated A(1), A(2A), A(2B) and A(3). During the past decades, potent antagonists have been developed for each of these subtypes. Adenosine antagonists have been developed as potential therapeutic agents for CNS disorders, inflammatory diseases, asthma, kidney failure and ischaemic injuries. Structurally, antagonists can be classified as xanthines and non-xanthines. Many ligands that were previously considered selective at the ARs have been found to be less selective at human ARs and therapeutic potential may need to be re-evaluated. Due to the high lipophilicity and corresponding low water-solubility of many very potent adenosine antagonists, bioavailability is often very low. To address this problem, recent approaches have led to the development of water-soluble prodrugs that release highly potent antagonists in vivo with substantially improved bioavailability.