Vasopressin Receptor Antagonists, Heart Failure, and Polycystic Kidney Disease

• Published in: Annual review of medicine Vol. 66; no. 1; pp. 195 - 210
• Main Author: Torres, Vicente E
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 14.01.2015; Annual Reviews, Inc
• Subjects: Antagonist drugs; Antidiuretic Hormone Receptor Antagonists - therapeutic use; aquaretics; baroreceptors; Clinical trials; Drug therapy; Heart failure; Heart Failure - drug therapy; Humans; Kidney diseases; osmoreceptors; Polycystic Kidney Diseases - drug therapy; Receptors, Vasopressin; vaptans; vasopressin V1a receptor; vasopressin V2 receptor; Japan; baroreceptors; aquaretics; osmoreceptors; vaptans; vasopressin V2 receptor; vasopressin V1a receptor
• ISSN: 0066-4219; 1545-326X
• DOI: 10.1146/annurev-med-050913-022838

The synthesis of nonpeptide orally bioavailable vasopressin antagonists devoid of agonistic activity (vaptans) has made possible the selective blockade of vasopressin receptor subtypes for therapeutic purposes. Vaptans acting on the vasopressin V2 receptors (aquaretics) have attracted attention as a possible therapy for heart failure and polycystic kidney disease. Despite a solid rationale and encouraging preclinical testing, aquaretics have not improved clinical outcomes in randomized clinical trials for heart failure. Additional clinical trials with select population targets, more flexible dosing schedules, and possibly a different drug type or combination (balanced V1a V2 receptor antagonism) may be warranted. Aquaretics are promising for the treatment of autosomal dominant polycystic kidney disease and have been approved in Japan for this indication. More studies are needed to better define their long-term safety and efficacy and optimize their utilization.