Vasopressin Receptor Antagonists

Vasopressin Receptor Antagonists

1. Definition, terminology & place in therapy

• Vasopressin receptor antagonists ("vaptans") are orally or parenterally active, mostly nonpeptide drugs that competitively block arginine-vasopressin (AVP) at its G-protein–coupled receptors — principally the renal V₂ receptor — producing solute-free water diuresis (aquaresis) rather than natriuresis (KDT 8e Ch.43, p.642).
• The class is defined by its mechanism (V₂ ± V_1a blockade) and its signature renal effect: increased free-water clearance with little or no change in Na⁺/K⁺ excretion — distinguishing vaptans from classical diuretics, which are natriuretic (KDT 8e Ch.43, p.642).
• Terminology: KDT places these drugs under "Antidiuretics" only because the chapter centres on AVP physiology; mechanistically vaptans are anti-antidiuretics / aquaretics — they oppose AVP's antidiuretic action and raise urine volume (KDT 8e Ch.43, p.642).
• Members in clinical use / development: tolvaptan (oral, V₂-selective), conivaptan (IV, dual V_1a+V₂), mozavaptan (oral, V₂-selective; Japan), lixivaptan (oral, V₂-selective; investigational) (KDT 8e Ch.43, p.642).
• Primary therapeutic rationale: in states of inappropriately high circulating AVP with dilutional hyponatraemia (SIADH, heart failure, cirrhosis), AVP-driven V₂ activation causes water retention; antagonising V₂ excretes the retained free water and corrects serum Na⁺ (KDT 8e Ch.43, p.644).
• A second, distinct rationale exploits the role of V₂/cAMP signalling in cyst growth in autosomal dominant polycystic kidney disease (ADPKD): chronic V₂ blockade with tolvaptan slows total-kidney-volume growth and eGFR decline [PMID 18369330 — TEMPO 3:4; FDA JYNARQUE label].