Vascular Effects of RWJ‐676070, a Selective Combined V1a/V2 Vasopressin Receptor Antagonist

In recent years, several vasopressin antagonists have been developed that block V1 receptors either selectively or nonselectively.1,2 To date, one combined V1/V2 antagonist (primarily a V2 antagonist, as determined on the basis of human receptor binding data), conivaptan, has been approved for the treatment of euvolemic hyponatremia.3,4 We have previously shown that the vascular properties of a vasopressin V1 antagonist can be investigated safely and reliably in healthy subjects. We used the measurement of skin blood flow after intradermic injection of exogenous arginine vasopressin on a skin area prevasodilated with calcitonin gene–related peptide (CGRP).3,5 This technique enables the documentation of the dose-dependent effects of vasopressin or vasopressin antagonists. In this study, we have characterized the V1a pharmacodynamic profile of increasing doses of RWJ-676070, a new orally active dual V1a/V2 receptor antagonist, in healthy subjects.5 Clinical Pharmacology & Therapeutics (2009); 85, 2, 145–148 doi:10.1038/clpt.2008.217