Vasopressin V₂-receptor antagonists: Panaceas for hyponatremia?

The current treatment of hyponatremia is unsatisfactory and can be associated with significant morbidity. Vasopressin is inappropriately elevated in the majority of patients with hyponatremia and causes free water retention by stimulating V₂-receptors in the collecting ducts. Recently, orally active, nonpeptide, selective vasopressin V₂-receptor antagonists have been characterized and offer an exciting prospect for the treatment for hyponatremia. V₂-receptor antagonists are effective aquaretic agents, that are capable of increasing free water clearance and plasma sodium and might be useful in the treatment of hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone, heart failure, cirrhosis, and nephrotic syndrome. The rationale for their use and evidence from animal end human studies are discussed.