The Synergic In Vitro Tocolytic Effect of Nifedipine Plus Ritodrine on Human Myometrial Contractility.
Many pharmacological agents have been investigated to manage preterm labor; we postulate that a combination of tocolytic drugs may achieve a better effect in the prevention of uterine contractions without dose-dependent adverse effects. The aim of this study was to evaluate the inhibitory effect of dual combinations of tocolytics in vitro. Human myometrium was obtained during elective cesarean sections (term without labor; n = 40). Myometrial strips were placed in organ baths for the measurement of isometric tension. Contractile activity was induced by oxytocin (10-8mol/L), then a concentration-response curve to single or dual combinations of tocolytics was started. All studied tocolytics (nifedipine, ritodrine, nitroglycerin, atosiban, and NS-1619), when used alone, significantly inhibited myometrial contractions. When combined, nifedipine plus ritodrine produced a significantly greater inhibition of contractility than each drug alone in the midrange of concentrations. The combination of nifedipine plus nitroglycerin or nifedipine plus atosiban produced a significantly greater inhibition than nitroglycerin or atosiban alone but not greater than nifedipine. The combination of nifedipine plus NS-1619 (Ca+2-activated K+[BKCa] channel opener) reduced the inhibitory effect of each drug. We concluded that a selected combination of tocolytics (nifedipine plus ritodrine) produced a significantly greater inhibitory effect on contractility than each drug alone at intermediate concentrations. Thus, specific combinations of tocolytics with different intracellular signaling pathways may have a synergic effect constituting a provocative new option for preterm labor treatment.
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Jorge Andrés
JA
Carvajal
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
María José
MJ
Zambrano
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Nur Mónica
NM
Theodor
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Luis Emilio
LE
Moreno
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Thiare Rosario
TR
Olguín
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Paula Sofía
PS
Vanhauwaert
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Nevenka Belén
NB
Rojas
1 Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Ana María
AM
Delpiano
D001562:Benzimidazoles / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011247:Pregnancy; D012312:Ritodrine / Q000494:pharmacology*; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D001562:Benzimidazoles; D015149:Tocolytic Agents; C047046:atosiban; C086491:NS 1619; D012312:Ritodrine; D009543:Nifedipine; D014668:Vasotocin
human myometrium; nifedipine; ritodrine; tocolysis