Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: A multicenter effectiveness and safety study

Moutquin, Jean‐Marie; Sherman, Dan; Cohen, Howard; Mohide, Patrick; Hochner‐Celnikier, Drorith; Fejgin, Moshe D.; Liston, Robert; Dansereau, Jerome; Mazor, Moshe; Shalev, Eliezer; Boucher, Marc; Glezerman, Marek; Zimmer, Etan Z.; Rabinovici, Jaron

doi:10.1067/mob.2000.104950

Cited by 200 publications

(117 citation statements)

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“…However, these mechanisms share a common final pathway that results in uterine smooth muscle contractions. It is well known that oxytocin and prostaglandin F 2 a (PG F 2 a) induce pregnant uterine contractions (Akerlund et al 1987, Keirse 1992, Moutquin et al 2000. Therefore, these agents have been used clinically for induction of delivery or termination of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Role of protein kinase Cβ in rhythmic contractions of human pregnant myometrium

Yasuda

Nakamoto²,

Yasuhara³

et al. 2007

Reproduction

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To assess the role of protein kinase Cb (PKCb) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCb inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCb in the pregnant myometrium with that in the nonpregnant myometrium. The effects of LY333531 on the myometrial contractions were examined by measuring contractile activity (frequency and amplitude). PKCb in human myometrium was assessed at mRNA level using real-time PCR method. The characteristics of contractile activity were different between the pregnant and the nonpregnant myometrium. The amplitude of rhythmic contractions in the preterm and term myometrium was increased 2-to 2.5-fold when compared with that in the nonpregnant myometrium, but the frequency of rhythmic contractions was decreased by about half. LY333531 (10 K6 M) reduced the increased amplitude in the preterm and term myometrium by about 50%, and the inhibitory effects of LY333531 in the pregnant myometrium were significantly greater than that in the nonpregnant myometrium (about 50 vs 25%). However, the frequency in the pregnant and nonpregnant myometrium was not influenced by LY333531. Real-time PCR revealed a significant, five-to sevenfold increase in the expression of PKCb mRNA in the preterm and term myometrium when compared with the nonpregnant myometrium. These findings suggest that the increased amplitude of human myometrial contractions during pregnancy is related to the increased level of PKCb. A PKCb inhibitor may reduce preterm uterine contractions and prevent preterm delivery.

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Section: Introductionmentioning

confidence: 99%

Role of protein kinase Cβ in rhythmic contractions of human pregnant myometrium

Yasuda

Nakamoto²,

Yasuhara³

et al. 2007

Reproduction

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“…Recently, the injectable peptide OT-R antagonist atosiban has shown efficacy for imminent preterm birth. However, it is inconvenient to use, because it requires constant infusion and is limited to the short-term treatment (1-2 days) of the acute phase of preterm labor (Moutquin et al, 2000;Romero et al, 2002). This drug also has activity against the V1a receptor.…”

mentioning

confidence: 99%

Pharmacology of (2S,4Z)-N-[(2S)-2-Hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a New Potent and Selective Nonpeptide Antagonist of the Oxytocin Receptor

Cirillo¹,

Tos²,

Schwarz³

et al. 2003

J Pharmacol Exp Ther

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We have discovered a new, potent, selective, and orally active oxytocin receptor antagonist, (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino)-1-[(2Ј-methyl[1,1Ј-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide (compound 1).We report the biochemical, pharmacological, and pharmacokinetic characterization in vitro and in vivo of this compound. Premature birth is a major problem in obstetrics affecting about 10% of all births and being the largest cause of perinatal morbidity and mortality. The impact on society is significant in terms of costs of neonatal intensive care and for the emotional and social stress to the family. The physiopathology of human preterm labor is complex and multifactorial. Preterm increase of uterine activity is a common complication of pregnancy and accounts for many cases of preterm labor. Pharmacological interventions aimed at maintaining uterine quiescence (tocolysis) have been, and are likely to remain, the cornerstone of pharmaceutical management of preterm labor. However, current tocolytic agents (␤-mimetics, magnesium sulfate, calcium channel blockers, or prostaglandin synthesis inhibitors) suffer from a minimal effectiveness and show important fetal and maternal side effects. Therefore, it is obvious that a safe and effective oral treatment delaying spontaneous preterm birth would have tremendous clinical benefits.The peptide hormone oxytocin (OT) is a potent contractor of the human uterus. OT mediates its effect through activation of the G protein-coupled oxytocin receptor (OT-R) that is expressed in myometrial cells. OT-R is coupled to phospholipase C activation, leading to intracellular synthesis of inositol phosphates and mobilization of calcium. In turn, the rise in intracellular calcium concentration promotes a cascade of events, including phosphorylation of myosin, that then acts on actin and induces uterine muscle cell contraction. Before onset of labor and in the term myometrium, the OT-R density Article, publication date, and citation information can be found at

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“…[26][27][28][29] Ritodrine had large effects while atosiban showed no significant influences on the cardiovascular system. Like other studies cardiac index increased with ritodrine [30;31] and remained unchanged with atosiban.…”

Section: Discussionmentioning

confidence: 99%