Vasopressin V2 receptor antagonists.
Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and disorders of water retention such as congestive heart failure and cirrhosis is a common problem encountered in the care of the medical patient. Thus far, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been suboptimal. The development of nonpeptide AVP V2 receptor antagonists represents a promising treatment option to directly antagonize the effects of elevated plasma AVP concentrations by increasing the water permeability of renal collecting tubules, thereby promoting excretion of retained water and normalizing hypoosmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies in the development of several nonpeptide AVP V2 receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds, as well as their vascular effects, are also described.
Wong
L L
LL
Department of Medicine, Division of Endocrinology and Metabolism, 232 Building D, Georgetown University School of Medicine, 4000 Reservoir Road NW, Washington, DC 20007, USA.
Verbalis
J G
JG
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D002986:Clinical Trials as Topic; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000188:drug therapy / Q000503:physiopathology; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy* / Q000503:physiopathology
D065092:Antidiuretic Hormone Receptor Antagonists