A double-blind placebo-controlled trial of an oxytocin-receptor antagonist (antocin) in the treatment of preterm labor

Sibai, BM; Romero, Rossana; Sánchez-Ramos, Luis; Valenzuela, G.; Veille, Jean-Claude; Tabor, Bannie L.; Morrison, John C.; Varner, M.W.; Goodwin, Tyler M.; Menard, Kathryn; Lane, Roger; Smith, Janice; Creasy, George W.

doi:10.1016/s0002-9378(97)80072-5

Cited by 10 publications

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“…[1][2][3] Drugs used to treat preterm labor, such as prostaglandin synthesis inhibitors, calcium channel antagonists and ␤-adrenoceptor agonists, have only short-lived effects or have potential side effects for mother and fetus. 4,5 Agents that have been used more recently, such as oxytocin receptor antagonists 6 and nitric oxide (NO) donors, 7 are currently the focus of intensive research, but early reports suggest that they will not confer major benefits. One reason there is no effective method of treating preterm labor is our limited knowledge of the mechanisms that control myometrial quiescence during pregnancy and its contractile state in normal and preterm labor.…”

mentioning

confidence: 99%

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Barber¹,

Robson

Lyall³

1999

The American Journal of Pathology

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The nitric oxide (NO)-cGMP pathway has been proposed as a mechanism for relaxation of myometrium during pregnancy and as a modulator of labor. Carbon monoxide (CO) , produced by hemeoxygenases (HO-1 and HO-2) , also activates soluble guanylate cyclase to increase cGMP. A recent study reported a large increase in HO-1 and HO-2 proteins during pregnancy , suggesting that the HO-CO pathway may be important in the maintenance of uterine quiescence during pregnancy. In this study we used Western blotting , reverse transcription-polymerase chain reaction , and immunohistochemistry to determine HO-1 and HO-2 expression in nonpregnant , pregnant, and laboring myometrium. Immunolocalization of HO was also compared with endothelial and inducible nitric oxide synthases (eNOS and iNOS). In contrast to HO-1 protein , which was not detected in myometrium , HO-2 protein and mRNA were constitutively expressed , although there were no differences in expression between the groups. eNOS was expressed in endothelial cells but not in myometrial smooth muscle. iNOS protein was not detected in myometrium. These data do not support an up-regulation of HO-1 and HO-2 during pregnancy and are not consistent with a role for NO or a major role for CO in human myometrial quiescence. Our results are also in keeping with HO-2 being an noninducible protein. Although spontaneous preterm birth (delivery before 37 weeks) accounts for 5 to 10% of all births, it is associated with up to 70% of neonatal deaths. It is also responsible for up to 75% of neonatal morbidity with considerable long-term morbidity in the child. 1-3 Drugs used to treat preterm labor, such as prostaglandin synthesis inhibitors, calcium channel antagonists and ␤-adrenoceptor agonists, have only short-lived effects or have potential side effects for mother and fetus. 4,5 Agents that have been used more recently, such as oxytocin receptor antagonists 6 and nitric oxide (NO) donors, 7 are currently the focus of intensive research, but early reports suggest that they will not confer major benefits. One reason there is no effective method of treating preterm labor is our limited knowledge of the mechanisms that control myometrial quiescence during pregnancy and its contractile state in normal and preterm labor. 8,9 NO, produced by the enzyme nitric oxide synthase (NOS), binds to the heme prosthetic moiety of the soluble guanylate cyclase, leading to increased cGMP production and smooth muscle relaxation. Carbon monoxide (CO) also binds to heme and activates soluble guanylate cyclase. 10 Discrepancies in localization of NOS and guanylate cyclase in the brain indicate that a substantial portion of guanylate cyclase may not serve as a target for NO. 11 CO is produced by heme oxygenase (HO), a microsomal enzyme that oxidatively cleaves heme, a prooxidant, to produce biliverdin and CO in the presence of NADPH-cytochrome P 450 reductase and NADPH. 12 HO consists of two homologous isoenzymes: HO-1, which is inducible, and HO-2, which is constitutive. 13,14 HO-1 is expressed at high concent...

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confidence: 99%

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Barber¹,

Robson

Lyall³

1999

The American Journal of Pathology

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“…Most available tocolytic agents used for preterm labor, such as adrenergic receptor agonists (e.g., ritodrine), magnesium sulfate (e.g., MgSO 4 ), calcium channel blockers (e.g., nifedipine), and oxytocin antagonists (e.g., atosiban), had no effect (or even caused adverse effects in some cases) on neonatal outcomes [5][6][7][8][9][10]. In contrast, recent studies in humans and animals showed that transdermal nitroglycerin (GTN) could reduce serious maternal and fetal complications [11].…”

Section: Introductionmentioning

confidence: 99%

Cost-Effectiveness of Transdermal Nitroglycerin Use for Preterm Labor

et al. 2011

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Oxytocin receptor antagonists for inhibiting preterm labour

Papatsonis

Flenady

Cole

et al. 2005

Cochrane Database of Systematic Reviews

154

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Analysis 1.3. Comparison 1 Atosiban versus placebo, Outcome 3 Neonatal death (up to 28 days).. .. .. .. Analysis 1.4. Comparison 1 Atosiban versus placebo, Outcome 4 Infant death (up to 12 months).. .. .. .. Analysis 1.5. Comparison 1 Atosiban versus placebo, Outcome 5 Preterm birth less than 28 weeks' gestation.. .. Analysis 1.6. Comparison 1 Atosiban versus placebo, Outcome 6 Preterm birth less than 37 weeks' gestation.. .. Analysis 1.7. Comparison 1 Atosiban versus placebo, Outcome 7 Birth within 48 hours of initiation of treatment. .

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A double-blind placebo-controlled trial of an oxytocin-receptor antagonist (antocin) in the treatment of preterm labor

Cited by 10 publications

References 0 publications

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Cost-Effectiveness of Transdermal Nitroglycerin Use for Preterm Labor

Oxytocin receptor antagonists for inhibiting preterm labour

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