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Chapter: Basic & Clinical Pharmacology : Diuretic Agents

Adenosine A1-Receptor Antagonists

In addition to their potentially beneficial effect in preventing tubuloglomerular feedback .

ADENOSINE A1-RECEPTOR ANTAGONISTS

In addition to their potentially beneficial effect in preventing tubuloglomerular feedback (, under Heart Failure), adenosine receptor antagonists interfere with the activation of NHE3 in the PCT and the adenosine-mediated enhancement of collecting tubule K+ secretion. Thus, adenosine receptor antagonists should be very useful diuretics.Caffeine and theophylline have long been known to be weak diuretics because of their modest and nonspecific inhibition of adenosine receptors. A more selective A1 antagonist, rolofylline, was recently withdrawn from study because of CNS toxicity and unexpected negative effects on GFR. However, newer adenosine inhibitors that are much more potent and more specific have been synthesized. Several of these (Aventri [BG9928], SLV320, and BG9719) are under study and if found to be less toxic than rolofylline, may become available as diuretics that avoid the diuretic effects of K+ wasting and decreased GFR resulting from tubuloglomerular feedback.


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Basic & Clinical Pharmacology : Diuretic Agents : Adenosine A1-Receptor Antagonists |


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