Oxytocin receptor blockade: a new principle in the treatment of preterm labor?
The concentration of myometrial and decidual oxytocin receptors increases dramatically in normal women in late pregnancy, causing enhanced uterine sensitivity to physiologic levels of oxytocin. Similar increase in myometrial oxytocin receptors has been found in women in preterm labor, indicating a role for oxytocin also in idiopathic preterm labor. A newly synthesized oxytocin analogue, 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, has been found to be a competitive inhibitor of oxytocin. The present study was conducted to test its efficacy in suppressing uterine contractions during preterm labor in women. Twelve patients with established, uncomplicated preterm labor between 27 and 33 weeks of gestational age were given intravenous infusions of the analogue for 1.5 to 13 hours during continuous external cardiotocographic monitoring. In nine patients inhibition of uterine contractions was achieved and further progression in cervical scores was arrested. In three patients, all at 27 weeks of gestational age, no significant tocolytic effect was observed during a 1.5-hour infusion of the analogue and the patients were then given ritodrine intravenously. No side effects were observed in any of the patients. These preliminary findings support the concept that an increased concentration of uterine oxytocin receptors is an important etiologic factor in uncomplicated preterm labor and therefore oxytocin receptor blockade may be a therapeutic alternative for this condition.
Andersen
L F
LF
Department of Obstetrics and Gynecology, Hvidovre Hospital, University of Copenhagen, Denmark.
Lyndrup
J
J
Akerlund
M
M
Melin
P
P
D000328:Adult; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011945:Receptors, Angiotensin / Q000187:drug effects; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives*
D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D010121:Oxytocin; D014668:Vasotocin