Profile of an oxytocin antagonist, RWJ 22164 for treatment of preterm labor in laboratory models of uterine contractility.
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.
Demarest
K T
KT
R.W. Johnson Pharmaceutical Research Institute, Ortho Pharmaceutical Corporation, Raritan, New Jersey 08869.
Hahn
D W
DW
Ericson
E
E
Capetola
R J
RJ
Fuchs
A R
AR
McGuire
J L
JL
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*
D015149:Tocolytic Agents; C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin