Arginine vasopressin receptor antagonists (vaptans): pharmacological tools and potential therapeutic agents

• Published in: Drug discovery today Vol. 15; no. 19; pp. 826 - 841
• Main Authors: Veeraveedu, Punniyakoti T., Palaniyandi, Suresh S., Yamaguchi, Ken’ichi, Komai, Yutaka, Thandavarayan, Rajarajan A., Sukumaran, Vijayakumar, Watanabe, Kenichi
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2010; Elsevier
• Subjects: Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin - metabolism; Benzazepines - pharmacology; Benzazepines - therapeutic use; Biological and medical sciences; Clinical Trials as Topic; Drug Evaluation, Preclinical; General pharmacology; Heart Failure - drug therapy; Humans; Hyponatremia - drug therapy; Hyponatremia - etiology; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Receptors, Vasopressin - metabolism; Sodium Potassium Chloride Symporter Inhibitors - pharmacology; Pharmaceutical technology; Treatment; Arginine; Aminoacid; Antagonist; Vaptan derivatives; Vasopressin receptor
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2010.08.001

The development of various non-peptide vasopressin receptor antagonists presents a new area of drug discovery for the treatment of heart failure and hyponatremia of multiple causes.
Arginine vasopressin (AVP) attracted attention as a potentially important neurohormonal mediator of the heart failure (HF) syndrome and hyponatremic states in humans because AVP influences renal handling of free water, vasoconstriction and myocyte biology through activation of V
2 and V
1a receptors. Current research is exploring V
2- and dual V
1a/V
2 receptor antagonism for the treatment of hyponatremia, as well as for the congestion and edema associated with chronic HF, because vasopressin receptor antagonists might offer benefits in comparison with conventional loop diuretics. The purpose of this review is to update the current status of experimental and clinical studies with available vasopressin receptor antagonists (conivaptan and tolvaptan) and their potential role in the treatment of HF and hyponatremia of multiple causes.