title: Delay of preterm birth in sheep by THG113.31, a prostaglandin F2alpha receptor antagonist.
abstract: OBJECTIVE
  A novel prostaglandin F2alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep.
  
  
  METHODS
  We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F2alpha and E2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth.
  
  
  RESULTS
  THG113.31 suppressed the amplitude of prostaglandin F2alpha, but not prostaglandin E2-induced contractions of both circular and longitudinal myometrium (P<.01). The times to delivery after RU486 were 34.8+/-1.1 hours (saline solution) and 41.9+/-0.5 hours (THG113.31; P<.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (PaO2 , PaCO2 , pH, or SaO2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2alpha metabolite concentrations rose similarly in both groups.
  
  
  CONCLUSIONS
  THG113.31 specifically suppresses prostaglandin F2alpha-induced myometrial contractility and delays delivery.
authors: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors: Jonathan J
authors: JJ
authors: Hirst
authors: Helena C
authors: HC
authors: Parkington
authors: I Ross
authors: IR
authors: Young
authors: Hannah K
authors: HK
authors: Palliser
authors: Krishna G
authors: KG
authors: Peri
authors: David M
authors: DM
authors: Olson
mesh_terms: D000818:Animals; D036861:Delivery, Obstetric; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D004576:Electromyography; D005260:Female; D005312:Fetal Blood; D006854:Hydrocortisone / Q000097:blood; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D047928:Premature Birth / Q000517:prevention & control*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012756:Sheep; D013997:Time Factors; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000502:physiology
chemical_list: D010455:Peptides; D011980:Receptors, Progesterone; D011982:Receptors, Prostaglandin; C519378:THG113.31 peptide; D015149:Tocolytic Agents; C034671:prostaglandin F2alpha receptor; D015735:Mifepristone; D015237:Dinoprost; D015232:Dinoprostone; D006854:Hydrocortisone