Non-peptide arginine-vasopressin antagonists: the vaptans

• Published in: The Lancet (British edition) Vol. 371; no. 9624; pp. 1624 - 1632
• Main Authors: Decaux, Guy, Prof, Soupart, Alain, MD, Vassart, Gilbert, Prof
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 10.05.2008; Lancet; Elsevier Limited
• Subjects: Animals; Antidiuretic Agents - therapeutic use; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin - physiology; Arginine Vasopressin - therapeutic use; Benzazepines - adverse effects; Benzazepines - therapeutic use; Biological and medical sciences; Clinical Trials as Topic; Contraindications; Drug therapy; Effectiveness; General aspects; Hormones; Humans; Hyponatremia - drug therapy; Internal Medicine; Medical sciences; Mental disorders; Models, Molecular; Mortality; Patients; Pituitary gland; Plasma; Receptors, Vasopressin - physiology; Rodents; Studies; Medicine; Arginine; Peptides; Aminoacid; Neurohypophyseal hormone; Antagonist; Neuropeptide; Vaptan derivatives; Vasopressin
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(08)60695-9

Summary Arginine-vasopressin is a hormone that plays an important part in circulatory and water homoeostasis. The three arginine-vasopressin-receptor subtypes—V1a, V1b, and V2—all belong to the large rhodopsin-like G-protein-coupled receptor family. The vaptans are orally and intravenously active non-peptide vasopressin receptor antagonists that are in development. Relcovaptan is a selective V1a-receptor antagonist, which has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhoea, and tocolysis. SSR-149415 is a selective V1b-receptor antagonist, which could have beneficial effects in the treatment of psychiatric disorders. V2-receptor antagonists—mozavaptan, lixivaptan, satavaptan, and tolvaptan—induce a highly hypotonic diuresis without substantially affecting the excretion of electrolytes (by contrast with the effects of diuretics). These drugs are all effective in the treatment of euvolaemic and hypervolaemic hyponatraemia. Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia.