Pharmacology of vasopressin antagonists.

Congestive heart failure (CHF) is characterized by fluid and water retention, which frequently is a therapeutic challenge. Most conventional diuretics act primarily as saluretics, i.e. they inhibit renal tubular electrolyte reabsorption, which due to osmotic pressure promotes excretion of isotonic fluid. Arginine vasopressin (AVP) via the V(1A) receptor vasoconstricts and via the V(2) receptor promotes water reabsorption in the renal collecting duct by inserting aquaporin-2 water channels into the luminal membrane. Novel V(2) receptor antagonists act as powerful aquaretics, i.e. they excrete free water. We review the pharmacology of non-selective V(1A)/V(2) receptor antagonists and selective V(2) receptor antagonists currently in clinical development.