Vasopressin Receptor Antagonists

Introduction & definition

• Vasopressin receptor antagonists ("vaptans") are mostly nonpeptide, orally or parenterally active drugs that competitively block arginine-vasopressin (AVP) at its GPCR receptors — principally the renal V₂ receptor — producing solute-free water diuresis (aquaresis) rather than natriuresis.
• Signature effect — they increase free-water clearance with little or no change in Na⁺/K⁺ excretion, distinguishing them from classical diuretics, which are natriuretic. Mechanistically they are anti-antidiuretics / aquaretics — they oppose AVP's antidiuretic action and raise urine volume (KDT lists them under "Antidiuretics" only because the chapter centres on AVP physiology).
• Members in use / development — tolvaptan (oral, V₂-selective; class prototype), conivaptan (IV, dual V_1a+V₂), mozavaptan (oral, V₂-selective; Japan) and lixivaptan (oral, V₂-selective; investigational).
• Two therapeutic rationales — (1) in states of inappropriately high AVP with dilutional hyponatraemia (SIADH, heart failure, cirrhosis), V₂ blockade excretes retained free water and corrects serum Na⁺; (2) chronic V₂/cAMP blockade slows cyst growth in ADPKD [FDA JYNARQUE; PMID 23121377].
• Exam framing — vaptans are the canonical example of "aquaretics" — a high-yield contrast against loop/thiazide diuretics (natriuretic) and against desmopressin (a V₂ agonist, opposite goal).