J. Donald Albright* and Peter S. Chan Pages 615 - 632 ( 18 )
Arginine. vasopressin (AVP) (antidiuretic harmone) exerts its action through three membrane-bound G-protein-coupled receptor subtypes (V1a and V2, and V3). The vasopressin-induced antidiuresis (via V2 receptors coupled to aquaporins) helps maintain normal plasma osmolality and salt (NaCl) balances. The human V1a and V2, and V3(V 1b) recep receptors and water selective membrane proteins (aquaporins) in the kidney have been cloned. Recent advances are the discovery and development of selective non-peptide antagonists (without agonist activity) that have been shown to be aquaretic agents in animals and humans. This review covers the characterization of vasopressin receptors V1a and V2, and V3 (V1b) (function, cloning, species variations, molecular modeling) and the discovery of non-peptide small molecules (of diverse structural types) that are potent AVP receptor antagonists. Animal and clinical studies of non-peptide AVP antagonists OPC-21268, OPC-31260, SR-49059, YM087 and VPA-985 are reported.