Vasopressin V2 receptor antagonists

Hyponatremia. due to the syndrome of inappropriate antidiuretic hormone sec retion (SLA-DH) and disorders of water retention such as congestive heart f ailure and cirrhosis is a common problem encountered in the care of the med ical patient. Thus far, available treatment modalities for disorders of exc ess arginine vasopressin (AVP) secretion or action have been suboptimal. Th e development of nonpeptide AVP V2 receptor antagonists represents a promis ing treatment option to directly antgonize the effects of elevated plasma A VP concentrations by increasing the water permeability of renal collecting tubules, thereby promoting excretion of retained water and normalizing hypo osmolar hyponatremia. In this review, SIADH and other water retaining disor ders are briefly discussed, after which the published preclinical and clini cal studies in the development of several nonpeptide AVP V2 receptor antago nists are summarized. The likely therapeutic indications and potential comp lications of these compounds, as well as their vascular effects, are also d escribed. (C) 2001 Elsevier Science BY. All rights reserved.