Arrest of preterm labor in rat and mouse by an oral and selective nonprostanoid antagonist of the prostaglandin F2alpha receptor (FP).
OBJECTIVE
The purpose of this study was to assess the tocolytic effect of AS604872, an orally active, potent, and selective prostanoid prostaglandin F2alpha receptor (FP) antagonist.


METHODS
Compound AS604872 was characterized and tested for its ability to block uterine contraction and delay preterm parturition in rodent models.


RESULTS
AS604872 inhibited spontaneous uterine contractions in pregnant rat near term. In pregnant mouse, AS604872 delayed parturition induced by either the antiprogesterone RU-486 or the endotoxin lipopolysaccharide. Pups from treated mothers were delivered alive. The efficacy of AS604872 was superior to the beta-mimetic drug ritodrine. Combination of AS604872 and ritodrine showed an additive inhibitory effect on spontaneous uterine contractions in rat.


CONCLUSIONS
A selective antagonist of the FP receptor suppresses uterine contractility and delays labor. Our findings identify a new potential modality for the pharmacological management of preterm labor.
Cirillo
Rocco
R
Istituto di Ricerche Biomediche A. Marxer. Merck Serono, Colleretto Giacosa, Italy.
Tos
Enrico Gillio
EG
Page
Patrick
P
Missotten
Marc
M
Quattropani
Anna
A
Scheer
Alexander
A
Schwarz
Matthias K
MK
Chollet
André
A
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012312:Ritodrine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D015149:Tocolytic Agents / Q000494:pharmacology*; D016896:Treatment Outcome; D014590:Uterine Contraction / Q000187:drug effects*
C522100:AS604872; D001713:Biphenyl Compounds; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D015149:Tocolytic Agents; C034671:prostaglandin F2alpha receptor; D015735:Mifepristone; D012312:Ritodrine