Molecular pharmacology of AVP and OT receptors and therapeutic potential

Classically, vasopressin (AVP) and oxytocin (OT) receptors were defined on the basis of the second messenger system coupled to the receptors and the affinity of a series of AVP and OT analogues with enhanced selectivity for a certain receptor type. These classification criteria have led to the distinction of vasopressin V-1a, V-1b and V-2 and oxytocin receptors. Recent reports on novel vasopressin analogues that exhibit selective vasodepressor agonistic activity suggest the presence of an as yet uncharacterized new vasopressin receptor, as well. Molecular cloning of this family has confirmed that vasopressin/oxytocin receptor subtypes are members of the G-protein-coupled receptor superfamily. Several vasopressin agonists have been developed that may be of potential therapeutic interest. AVP analogues combining high vasopressor potency and specificity with long-acting effects could be of clinical value in hemorrhage and circulatory disorders like hypertension. AVP and OT antagonists have been widely used as pharmacological tools in studies on the physiological and pathophysiological roles of AVP and OT and in receptor localization and characterization studies. While potent and selective V-1a, V-2 and OT antagonists have been developed, there is still a significant need for potent and selective V-1b antagonists. In the future, data will undoubtedly emerge from structure-activity relationships which have been greatly facilitated by the use of human receptors expressed in heterologous systems. (C) 1999 Prous Science. All rights reserved.