Evaluation of 1-deamino-[D-Tyr(Oethyl)2, Thr4, Orn8] vasotocin, an oxytocin antagonist, in animal models of uterine contractility and preterm labor: a new tocolytic agent.
We attempted to characterize the ability of a new oxytocin derivative, 1-deamino[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin (ORF 22164), to antagonize the action of oxytocin in several in vitro and in vivo animal models of uterine hyperactivity. In these studies, the derivative was found to be a specific competitive inhibitor of oxytocin-induced contractions of pregnant guinea pig uterus in vitro. In addition, its intravenous administration induced a dose-dependent inhibition of oxytocin-induced uterine contractions in situ. Finally, like ritodrine, the drug induced a dose-dependent delay of ongoing labor in rats. These results suggest that 1-deamino-[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin, unlike ritodrine, is a potent and specific antagonist of oxytocin-induced uterine contractions and thus may have potential clinical utility in the treatment of preterm labor.
Hahn
D W
DW
Research Laboratories, Ortho Pharmaceutical Corporation, Raritan, NJ 08869.
Demarest
K T
KT
Ericson
E
E
Homm
R E
RE
Capetola
R J
RJ
McGuire
J L
JL
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; 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; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin