Investigational vasopressin receptor modulators in the pipeline

The vasopressin system is complex and interacts with the central nervous, cardiovascular, renal, and hematological systems. Vasopressin plays an important role in the control of blood osmolarity and vascular tone, but is also involved in many other physiological events, which are mediated mainly via three types of vasopressin receptor: V1R, V2R, and V3R. V1R primarily mediate the vascular, and V2R the aquaretic, effects of vasopressin. Vasopressin may also interact with other receptors, like adrenergic and angiotensin-II receptors, or with distinct biological pathways, including those of nitric oxide and the K(ATP) channel. There are numerous clinical situations where vasopressin receptor modulators (agonists or antagonists) could be used. Currently, vasopressin and terlipressin are most commonly used to stimulate V1R in vasodilatory shock and cardiac arrest, while desmopressin, a synthetic analogue of vasopressin, acts on V2R; but new molecules are becoming available in the treatment of inappropriate antidiuretic hormone (ADH) secretion.