Endothelin receptors: receptor classification, novel receptor antagonists, and potential therapeutic targets.

The development of endothelin receptor antagonists has progressed rapidly since the initial discovery of endothelin. Highly potent, orally active nonpeptide endothelin receptor antagonists have been identified, and are being used as pharmacological tools to elucidate the role of endothelin in pathological disorders. Subtype selective endothelin receptor antagonists will also be useful in understanding the physiological and pathological roles of the different subtypes of the endothelin receptors. The selectivity profile for the ideal endothelin receptor antagonist is presently unknown, and it may actually be that the optimal profile for a compound may depend on the clinical indication. In the near future, data from clinical trials with endothelin receptor antagonists will become available and will help to establish the role of endothelin in the etiology of human disease, as well as to provide valuable information concerning the optimum endothelin receptor subtype selectivity for antagonists needed for therapeutic agents.