Vasopressin V2 receptor antagonists.
Hyponatremia, whether due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or disorders of water retention such as congestive heart failure and cirrhosis, is a very common problem encountered in the care of medical patients. To date, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been limited and suboptimal. The recent discovery and development of nonpeptide AVP V(2) receptor antagonists represents a promising new treatment option to directly antagonize the effects of elevated plasma AVP concentrations at the level of the renal collecting ducts. By decreasing the water permeability of renal collecting tubules, excretion of retained water is promoted, thereby normalizing or improving hypo-osmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies of several nonpeptide AVP V(2) receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds are also described.
Verbalis
J G
JG
232 Building D, Division of Endocrinology and Metabolism, Georgetown University School of Medicine, 4000 Reservoir Road NW, Washington DC 20007, USA. verbalis@georgetown.edu
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000188:drug therapy; D017483:Receptors, Vasopressin / Q000145:classification
D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin