Endothelin receptor antagonists: current status and perspectives.

Endothelin (ET) receptor antagonists have been proposed for the treatment of a variety of disorders where ET may act as a pathogenic mediator. The rationale is very strong in certain diseases, where ET concentrations are increased and where ET receptor antagonists have shown efficacy in experimental conditions. However, clinical studies are needed to prove that this approach is effective in the clinical setting. Because there are still very few ET receptor antagonists in clinical development, proof of concept studies in clinical situations have been performed only in a small number of indications. We describe here the preclinical and clinical results obtained with the first orally active ET receptor antagonist in three therapeutic fields, congestive heart failure, systemic hypertension and cerebral vasospasm. The encouraging clinical results obtained support a further clinical development of ET receptor antagonists in these three indications.