Nonpeptide vasopressin antagonists: A new group of hormone blockers entering the scene

Summary

After the story of success of hormone blockers for cate-cholamines, aldosterone and angiotensin 11 and their successful implementation into clinical practice another endocrine cardiovascu-lar system has come into focus. It has long been known, that the hormone vasopressin plays an important role in peripheral vaso-constriction, hypertension and in several disease conditions with dilutional hyponatremia in edematous disorders, like congestive heart failure, liver cirrhosis, SIADH and nephrotic syndrome. A series of orally active nonpeptide antagonists against the vasopres-sin receptor subtypes has recently been synthesized and is now under intensive examination. Nonpeptide V_1a-receptor specific antagonists, OPC 21268 and SR 49059, nonpeptide V₂-receptor specific antagonists, SR 121463 A and VPA 985, and combined V_1a-/V₂-receptor antagonists, OPC 31260 and YM 087, have become available for clinical research. AVP-V₂-receptor antagonists lead to a dose-dependent diabetes insipidus in animals and man. The term aquaretic drugs (aquaretics) has been coined for these drugs to highlight their different mechanism compared to the saluretic diuretic furosemide. V_1a-receptor antagonists might offer new therapeutic advantages in the treatment of vasoconstriction and hypertension. Combined V_1a-/V₂-receptor antagonists might be beneficial in the treatment of congestive heart failure. Early results are promising and now need to be confirmed in large clinical studies.

Key words

Nonpeptide vasopressin antagonists - dilutional hyponatremia - SIADH - liver cirrhosis - congestive heart failure