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

After the story of success of hormone blockers for catecholamines, aldoster one and angiotensin II and their successful implementation into clinical pr actice another endocrine cardiovascular system has come into focus. It has long been known, that the hormone vasopressin plays an important role in pe ripheral vasoconstriction, hypertension and in several disease conditions w ith dilutional hyponatremia in edematous disorders, like congestive heart f ailure, liver cirrhosis, SIADH and nephrotic syndrome. A series of orally a ctive nonpeptide antagonists against the vasopressin receptor subtypes has recently been synthesized and is now under intensive examination. Nonpeptid e V-1a-receptor specific antagonists, OPC 21268 and SR 49059, nonpeptide V- 2-receptor specific antagonists, SR 121463 A and VPA 985, and combined V-1a -/V-2-receptor antagonists, OPC 31260 and YM 087, have become available for clinical research. AVP-V-2-receptor antagonists lead to a dose-dependent d iabetes insipidus in animals and man. The term aquaretic drugs (aquaretics) has been coined for these drugs to highlight their different mechanism com pared to the saluretic diuretic furosemide. V-1a-receptor antagonists might offer new therapeutic advantages in the treatment of vasoconstriction and hypertension. Combined V-1a-/V-2-receptor antagonists might be beneficial i n the treatment of congestive heart failure. Early results are promising an d now need to be confirmed in large clinical studies.