Endothelin receptor antagonists: Current status and perspectives

Endothelin (ET) receptor antagonists have been proposed for the treatment o f a variety of disorders where ET may act as a pathogenic mediator. The rat ionale is very strong in certain diseases, where ET concentrations are incr eased and where ET receptor antagonists have shown efficacy in experimental conditions. However, clinical studies are needed to prove that this approa ch is effective in the clinical setting. Because there are still very few E T receptor antagonists in clinical development, proof of concept studies in clinical situations have been performed only in a small number of indicati ons. We describe here the preclinical and clinical results obtained with th e first orally active ET receptor antagonist in three therapeutic fields, c ongestive heart failure, systemic hypertension and cerebral vasospasm. The encouraging clinical results obtained support a further clinical developmen t of ET receptor antagonists in these three indications.