Adenosine A1 receptor antagonists in clinical research and development.
Selective adenosine A1 receptor antagonists targeting renal microcirculation are novel pharmacologic agents that are currently under development for the treatment of acute heart failure as well as for chronic heart failure. Despite several studies showing improvement of renal function and/or increased diuresis with adenosine A1 antagonists, particularly in chronic heart failure, these findings were not confirmed in a large phase III trial in acute heart failure patients. However, lessons can be learned from these and other studies, and there might still be a potential role for the clinical use of adenosine A1 antagonists.We review the role of adenosine A1 receptors in the regulation of renal function, and emerging data regarding the safety and efficacy of A1 adenosine receptor antagonists based on all available completed and reported clinical trials using A1 adenosine receptor antagonists. The majority of trials were done in heart failure patients. However, there is clear clinical evidence for a role of this new class in hepatorenal syndrome, hypotension on dialysis, and radiocontrast media-induced nephropathy.
Hocher
Berthold
B
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. berthold.hocher@roche.com
D000241:Adenosine / Q000502:physiology; D058916:Adenosine A1 Receptor Antagonists / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004232:Diuretics / Q000627:therapeutic use; D004351:Drug Resistance; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000503:physiopathology; D043682:Receptor, Adenosine A1 / Q000502:physiology
D058916:Adenosine A1 Receptor Antagonists; D004232:Diuretics; D043682:Receptor, Adenosine A1; D000241:Adenosine