Adenosine Receptor Ligands-Recent Developments Part I. Agonists

Developments in the field of adenosine receptor (AR) agonists of the past years are presented and discussed. Four different AR subtypes, A1, A2A, A2B, and A3, have been cloned from different species including the human receptors. Recombinant ARs expressed in permanent mammalian cell lines have found wide application in the screening of new ligands. Considerable differences are observed among data from different laboratories, using recombinant receptors for the assays. Reevaluation of compounds at all four receptor subtypes has shown that agonists that were believed to be selective for either A1 or A2A ARs may be potent A3 agonists and thus, non-selective. Potent and selective agonists for two of the AR subtypes, A1 and A3, have been developed. Truly selective A2A AR agonists, however, are presently not available. Potent or selective A2B agonists are still lacking. Since the treatment with AR agonists may lead to fast desensitization of the receptors, partial agonists, and indirect AR agonists, such as adenosine kinase inhibitors, or allosteric enhancers of adenosine binding, are being developed as site- and event-specific agents.