title: 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.
authors.affiliation: R.W. Johnson Pharmaceutical Research Institute, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869.
authors.forename: K T
authors.initials: KT
authors.lastname: Demarest
authors.forename: D W
authors.initials: DW
authors.lastname: Hahn
authors.forename: E
authors.initials: E
authors.lastname: Ericson
authors.forename: R J
authors.initials: RJ
authors.lastname: Capetola
authors.forename: A R
authors.initials: AR
authors.lastname: Fuchs
authors.forename: J L
authors.initials: JL
authors.lastname: McGuire
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D015149:Tocolytic Agents; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives*
chemical_list: D015149:Tocolytic Agents; C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin