Profile of an oxytocin antagonist, RWJ 22164 for treatment of preterm labor in laboratory models of uterine contractility

Abstract

An oxytocin antagonist, 1-deamino-[D-TYR(Oethyl)2,THR4,ORN8]oxytocin (RWJ 22164; dTVT), has recently been characterized in models of uterine contractility. Studies were undertaken to characterize the action of dTVT further on both oxytocin- and vasopressin-induced increases in uterine contractility both in vitro and in situ models and in a model of preterm labor. In these studies, dTVT was found to be a specific competitive inhibitor of both oxytocin- and vasopressin-induced contractions of both pregnant and nonpregnant guinea pig uterus in vitro. In situ, the intravenous administration of dTVT induced a dose-dependent inhibition of oxytocin- and vasopressin-induced contractions in a guinea pig model which measures uterine activity as changes in uterine perfusion pressure. Further studies demonstrated that the intravenous infusion of dTVT delays ongoing labor.