Tocolytic Research Articles

Cardiovascular Effects of KUR-1246, a New Tetrahydronaphthalen Derivative β2-Adrenoceptor Agonist and a Selective Uterine Relaxant

The aim of this study was to assess the cardiovascular effects of KUR-1246 (CAS 194785-31-4, (-)-bis(2-{[(2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl) phenyl] ethyl}amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy}-N,N-dimethylacetamide)monosulfate), a new beta2-adrenoceptor agonist tocolytic agent. In conscious dogs, the intravenous administration of KUR-1246 at 0.1 and 1 microg/kg had no effects on blood pressure, heart rate or femoral artery blood flow. KUR-1246 at 10 and 100 microg/kg significantly decreased blood pressure and increased heart rate. In the electrocardiograms, KUR-1246 did not affect QT intervals or QTc. In addition, the cardiac effects of KUR-1246 were evaluated in in vitro electrophysiological studies. KUR-1246 at 10 micromol/L did not affect action potential parameters (the maximal upstroke velocity, resting membrane potential, action potential amplitude and action potential durations) in isolated papillary muscles of guinea pigs or in the human ether-a-go-go related gene (HERG) tail current recorded from stably transfected human embryonic kidney (HEK) 293 cells. On the basis of these results, the effects of KUR-1246 in conscious dogs on the cardiovascular system appear to be limited to changes in blood pressure and heart rate. Therefore, KUR-1246 is unlikely to provoke ventricular arrhythmias by delaying the ventricular repolarization.

Use of isoxsuprine hydrochloride as a tocolytic agent in the treatment of preterm labour: a systematic review of previous literature.

The aim of this systematic review was to evaluate the efficacy of isoxsuprine (1-(4-hydroxyphenyl)-2-(1-methyl-2-phe-noxyethylamino)-1-propanol, CAS 395-28-8), a tocolytic agent used in both preterm labour and risk of abortion. Two analyses were conducted on data reporting the use of isoxsuprine in the prevention of preterm delivery. The first analysis examined two double-blind studies to determine the effect of isoxsuprine compared to placebo. The second analysis reviewed data from 25 publications containing individual and general patient data. Main outcome measures included delay of pregnancy and patient outcome. Analysis of double-blind studies demonstrated a positive outcome with isoxsuprine in 92% of cases compared to placebo control (44.4%, p < 0.001). This beneficial effect was maintained when either risk of abortion (92.5% in isoxsuprine treated compared to 46.4% in placebo, p < 0.001) or risk of premature delivery (89.5% in isoxsuprine treated compared to 29.4% in placebo, p < 0.001) was examined. Secondary analysis of individual patient data also revealed a beneficial effect of isoxsuprine in prolonging pregnancy in 54.5% of women at risk of abortion and in 82.3% of women at risk of premature delivery. Combination of individual and general data revealed a beneficial effect of isoxsuprine in 77.3% of cases at risk of abortion and 89% for risk of premature delivery. These findings provide preliminary evidence in favour of the effectiveness of isoxsuprine in prolonging pregnancy in women at risk of abortion or premature delivery.

Labor agency and the importance of the national scale: Emergent aquaculture unionism in Chile

In this article we argue for the continuing relevance of the national scale in understanding the geographies that shape and constrain labor agency. Recent contributions to labor geography have held that some of the central concepts used to understand the transformative capacities of labor, such as agency and scale, are under-theorized. On the basis of our study of the emergent labor movement in the Chilean aquaculture industry, we suggest that this field suffers from what we term “glocalocentrism”, which overshadows the fundamental importance of structures and processes that are primarily scaled nationally. With the labor repression of the Pinochet regime imprinted in current national institutions and organizational traditions, the aquaculture sector was able to develop in southern Chile from the early 1980s onwards, without a significant union movement to press workers’ claims, and it benefited from exploitative practices and low wages. The first company level unions did not appear until the late 1980s, and a national confederation of aquaculture unions was formed as late as 2006. After the outbreak of the ISA virus in 2007, thousands of workers were left unemployed, and the young union movement struggled for state intervention and programs, with some success. International networks brought attention to the issue, but structures and processes at the national level conditioned the possibilities for the emergent labor movement to press its claims successfully.

The Risk of Necrotizing Enterocolitis After Indomethacin Tocolysis

Tocolytic agents such as indomethacin are commonly used to prevent preterm delivery despite little evidence of proven benefit. Administration of postnatal indomethacin in preterm infants seems to be associated with an increased incidence of necrotizing enterocolitis (NEC). It has been hypothesized that antenatal indomethacin (AI), which readily crosses the placenta, may also increase the risk for NEC in preterm infants. This historical cohort study was designed to investigate the association between AI and NEC in preterm infants. The cohort included preterm infants at 23 to 32 weeks' gestational age without major congenital anomalies who had been admitted to a hospital NICU (neonatal intensive care unit) between 2004 and 2006. The investigators reviewed and abstracted maternal and neonatal data in medical records for preterm infants. Bivariate analyses, multivariate logistic regression, and propensity score analysis were used to determine the association between AI exposure within 15 days before delivery (predictor variable) and NEC (with NEC defined as modified Bell's stage 2a or higher) in the first 15 days of life (early NEC)—the primary outcome variable. Of the 628 infants who met inclusion criteria, 63 received AI and 28 developed early NEC. Exposure of mothers to AI was significantly associated with multiple gestation, white race, antenatal corticosteroids, and magnesium sulfate. In neonates, AI exposure was associated with lower birth weight and gestational age, a need for an umbilical arterial catheter, respiratory distress syndrome, postnatal vasopressors and antibiotics, patent ductus arteriosus, sepsis, NEC, intraventricular hemorrhage, and mortality. Multivariate logistic regression showed an association between AI exposure and the development of early NEC; the adjusted odds ratio was 7.193, with a 95% confidence interval of 2.514–20.575 (which represents a number needed to harm of 5). The association of AI and early NEC remained significant when multivariate logistic regression was repeated using AI exposure within 5 days before delivery as the predictor variable, when analyses were stratified according to gestational age, and on propensity score analysis. These findings show that multiple clinical factors, including AI, are associated with NEC in preterm infants in the first 15 days of life. Exposure to AI in preterm infants in the first 15 days of life may contribute to the morbidity and mortality of NEC.

Magnesium Sulfate Evokes Endothelium-Independent Relaxation in the Chicken Ductus Arteriosus

Background and aims: Magnesium sulfate (MgSO4) is widely used as tocolytic agent and for the prophylaxis of seizures in pre-eclampsia. Antenatal exposure to MgSO4 has been associated with a higher risk of patent DA in preterm infants. MgSO4 is a vasodilator and thus may exert a direct relaxant effect in the DA. Here we aimed to investigate the possible vasoactive effects of MgSO4 in the chicken DA.Design/Methods: Isolated rings of the DA from 15-d (E15) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Rings were precontracted with 21% O2, norepinephrine (NE, 1 μM) or KCl (62.5 mM).Results: MgSO4 (2.4-7.2 mM) elicited a concentration-dependent relaxation (mean maximal relaxation: 56.7%, SD 41.8; EC50: 2.9 mM, SD 0.3) of O2-induced active tone in E19 DA rings. MgSO4 also relaxed NE-contracted (with similar efficacy but lower potency than O2-contracted) and KCl-contracted (with lower efficacy and potency) E19 DA rings. MgSO4-induced relaxation of KCl-contracted DA rings was not significantly different between E15 and E19. Endothelium removal or the presence of the NO synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, the cyclooxygenase inhibitor indomethacin, or the sarcoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin did not significantly modify MgSO4-induced relaxation. The relaxant effect of MgSO4 was reversed by increasing the extracellular Ca2 concentration.Conclusions: MgSO4, at clinically relevant concentrations, induces endothelium-independent relaxation of chicken DA. This relaxant effect may be due to inhibition of Ca2+ entry from extracellular space.

Is worker repression risky? Foreign direct investment, labour rights and assessments of risk in developing countries

ABSTRACT Quantitative assessments of ‘country risk’ produced by private rating agencies have become influential among multinational firms considering investment in the developing world. This article considers whether developing countries exhibiting more labour rights violations are associated with higher risk ratings. It draws from existing literature on the determinants of foreign direct investment (FDI) and the relationship between labour rights and FDI to illuminate the ways in which labour repression may indicate increased risk for potential investors. It implements a set of time series of cross-sections models for 95 developing countries, from 1985 to 2003. These models present predictors of a long-established risk index, plus an additional latent risk measure created through factor analysis of three separate and distinct risk ratings. Results indicate a consistent association between increased labour rights violations and increased risk ratings. The article extends the analysis to highlight the heterogeneous nature of FDI and possible sector-specific relationships between labour rights and risk ratings. The paper argues that the economic profile of a country may condition the relationship between labour rights and risk ratings.

Comparative study of nifedipine and isoxpurine as tocolytics for preterm labor.

This study was done to compare isoxpurine hydrochloride and nifedipine as tocolytic drugs for preterm labor. A prospective cohort study of 832 antenatal women with preterm labor was conducted in the Department of Obstetrics & Gynecology. Out of 400 women found eligible for tocolysis, 200 were given isoxpurine hydrochloride while the other 200 were given nifedipine randomly. The data obtained was statistically analyzed on SPSS 10.0 of Windows 2003. Incidence of preterm labor was 22% while the incidence of preterm delivery was 20.9%. Nifedipine was twice more effective than isoxpurine hydrochloride as a tocolytic agent as a tocolytic agent (P value 0.006) while side effects were comparable (P value 0.133). In early-diagnosed preterm labor, nifedipine had higher efficacy than isoxpurine (P value 6.45×10(-6)) and also higher efficacy than its own in late diagnosed preterm labor (P value 2.08×10(-5)). There is a high incidence of preterm labor in India. Nifedipine is a better tocolytic drug than isoxpurine hydrochloride, especially when started with the earliest signs of preterm labor.

Allosteric interactions between the oxytocin receptor and the β2-adrenergic receptor in the modulation of ERK1/2 activation are mediated by heterodimerization

The oxytocin receptor (OTR) and the β2-adrenergic receptor (β2AR) are key regulators of uterine contraction. These two receptors are targets of tocolytic agents used to inhibit pre-term labor. Our recent study on the nature of OTR- and β2AR-mediated ERK1/2 activation in human hTERT-C3 myometrial cells suggested the presence of an OTR/β2AR hetero-oligomeric complex (see companion article). The goal of this study was to investigate potential allosteric interactions between OTR and β2AR and establish the nature of the interactions between these receptors in myometrial cells. We found that OTR-mediated ERK1/2 activation was attenuated significantly when cells were pretreated with the β2AR agonist isoproterenol or two antagonists, propranolol or timolol. In contrast, pretreatment of cells with a third β2AR antagonist, atenolol resulted in an increase in OTR-mediated ERK1/2 activation. Similarly, β2AR-mediated ERK1/2 activation was strongly attenuated by pretreatment with the OTR antagonists, atosiban and OTA. Physical interactions between OTR and β2AR were demonstrated using co-immunoprecipitation, bioluminescence resonance energy transfer (BRET) and protein-fragment complementation (PCA) assays in HEK 293 cells, the latter experiments indicating the interactions between the two receptors were direct. Our analyses suggest physical interactions between OTR and β2AR in the context of a new heterodimer pair lie at the heart of the allosteric effects.

Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics

The prostaglandin-F2α (PGF2α) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both Gαq- and Gα12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model ( Goupil ; et al. J. Biol. Chem. 2010 , 285 , 25624 - 25636 ). Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2α-induced myometrial contractions, potentiated the effect of PGF2α on Gαq-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the Gα12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.

Indomethacin in Pregnancy: Applications and Safety

Preterm labor (PTL) is a major cause of neonatal morbidity and mortality worldwide. Among the available tocolytics, indomethacin, a prostaglandin synthetase inhibitor, has been in use since the 1970s. Recent studies have suggested that prostaglandin synthetase inhibitors are superior to other tocolytics in delaying delivery for 48 hours and 7 days. However, increased neonatal complications including oligohydramnios, renal failure, necrotizing enterocolitis, intraventricular hemorrhage, and closure of the patent ductus arteriosus have been reported with the use of indomethacin. Indomethacin has been also used in women with short cervices as well as in those with idiopathic polyhydramnios. This article describes the mechanism of action of indomethacin and its clinical applications as a tocolytic agent in women with PTL and cerclage and its use in the context of polyhydramnios. The fetal and neonatal side effects of this drug are also summarized and guidelines for its use are proposed.

PRETERM LABOUR

Objective: To determine the effectiveness of transdermal patch of glyceryl trinitrate as tocolytic agent. Study design: Interventional- Quasi experimental study. Setting: Department of Obstetrics and Gynecology Unit- 1, Services hospital, Lahore. Duration with dates: One year (February 10, 2006 – February 10, 2007). Sample size: Fifty pregnant women with preterm labour were included in the study. Results: 54% of pregnant women were between G2 – G4. Majority (48%) of the women presented between 31 – 34 weeks of gestation. 46% of pregnant women had bishop score of 4 or more. 64% of patients found to have no risk factor for preterm labour. Majority (86%) responded after application of second patch (10 mg glyceryl trinitrate patch). 84% had no side effects. Local skin reaction (10%) and headache (4%) observed in few patients. 58% of pregnant women delivered after 48 hours and 78% of them delivered vaginally which was statically significant and majority of babies delivered weight more than 1.5 kg and with good Apgar score. Conclusions: It is concluded from the study that glyceryl trinitrate is a safer tocolytic, which has simple method of application; rapid onset of action with low cost, low risk from side effects and it does not require intensive monitoring.

4-Chloro-7-Trifluoromethyl-10H- Benzo[4,5]furo[3,2-b]Indole-1-Carboxylic Acid (TBIC), a Putative BKCa Channel Opener with Uterine Relaxant Activities

In the present study, we examined the uterine relaxant activity of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (TBIC), a putative opener of the large conductance Ca²⁺-activated K⁺ (BK_Ca) channel. TBIC concentration-dependently inhibited spontaneous uterine contractions (EC₅₀ = 4.63 µmol/l; E_max = 94.85 ± 1.85%; 100 µmol/l, n = 6). It also reduced contractions induced by oxytocin (EC₅₀ = 4.10 µmol/l; E_max = 84.3 ± 3.83%; 100 µmol/l, n = 6), prostaglandin F₂_α (EC₅₀ = 2.14 µmol/l; E_max = 73.70 ± 5.21%; 100 µmol/l, n = 6) and acetylcholine (EC₅₀ = 4.37 µmol/l; E_max = 83.67 ± 4.82; 100 µmol/l, n = 6). TBIC decreased KCl (20 mmol/l) -induced contractions (EC₅₀ = 3.04 µmol/l; E_max = 94.0 ± 3.12%; 100 µmol/l, n = 6) indicating its K⁺ channel opening activity. BK_Ca channel blockers penitrem A (100 nmol/l) and tetraethylammonium chloride (1 mmol/l) attenuated the inhibitory activities of TBIC (p < 0.001) but not other K⁺ channel blockers such as barium chloride and glibenclamide (K_IR and K_ATP channel blockers, respectively). These results demonstrate the uterine relaxant effects of TBIC in a mechanism of action largely referable to the potentiation of the BK_Ca channels. We have provided evidence for the potential use of TBIC as a tocolytic agent and support for the utility of BK_Ca channel openers in pathophysiologic conditions involving smooth muscle hyperactivity.

Ontogeny of sulfonylurea-binding regulatory subunits of KATP channels in the pregnant rat myometrium

ATP-sensitive potassium channels (K(ATP) channels) are composed of sulfonylurea receptors (SURs) and potassium inward rectifiers (Kir(6.x)) that assemble to form a large octameric channel. This study was designed to examine the expression and role of sulfonylurea-binding regulatory subunits 1 (SUR1 (ABCC8)) and 2 (SUR2 (ABCC9)) of the K(ATP) channels in the pregnant rat myometrium with particular regard to the contractility. RT-PCR and western blot analyses were performed to detect the presence of SUR1 and SUR2. The SUR1 levels were markedly increased in the early stages of pregnancy. The highest level was detected on day 6 of pregnancy, whereas in the late stages, the levels of SUR1 were significantly decreased. The SUR2 level remained unchanged throughout pregnancy. The SUR non-selective diazoxide and the SUR2-selective pinacidil inhibited oxytocin-induced contractions. Glibenclamide, a K(ATP) channel blocker, antagonized both pinacidil- and diazoxide-induced relaxations. It was established that SURs are responsible for pharmacological reactivity of K(ATP) channel openers. We conclude that both SURs are involved in the K(ATP) channel in the pregnant rat myometrium. It may further be concluded that 'pinacidil-like' K(ATP) channel openers may be of therapeutic relevance as tocolytic agents in the future.

Comparison of success rate of nifedipine, progesterone, and bed rest for inhibiting uterine contraction in threatened preterm labor

To compare the success rates and gestational ages at delivery of nifedipine, proluton depot administration as a tocolytic agent and bed rest groups to pregnant women with threatened preterm labor. A total of 150 pregnant women with threatened preterm labor between 28 and 35 weeks of gestation were enrolled in the study. All women underwent contraction inhibition randomly sorted into three groups. The first and second groups were inhibited with nifedipine and proluton depot, respectively. The third group was admitted for bed rest. Nifedipine, proluton depot and bed rest can be used to inhibit contraction in threatened preterm labor. However, when time-to-event test was used, nifedipine took the shortest time for contraction inhibition with statistical significance. Nifedipine, proluton depot and bed rest can be used successfully to inhibit contraction in threatened preterm labor. However, nifedipine took the shortest time to inhibit uterine contraction in threatened preterm labor.

The effectiveness of medical interventions aimed at preventing preterm birth: A literature review

Preterm birth is a significant global health problem with serious short and long term consequences. This paper reviews the research literature to answer the question how effective are the medical interventions that aim to reduce the rates of preterm birth? A systematic search was carried out in CINAHL, Cochrane, Medline and Embase in relation to following medical treatments aimed at preventing preterm births: anti-infective medications, tocolytics, progesterone and cervical cerclage. The research underpinning each type of intervention is critically analysed in order to establish the validity of knowledge claims that are made for each type of intervention. In relation to reducing the rates of preterm births, anti-infectives are only effective in the presence of known infection. Screening for infections during pregnancy is ineffective. Tocolytic agents are not effective in decreasing the preterm birth rates. Progesterone seems to be effective in a select group of pregnant women at higher risk of preterm birth. Cervical cerclage plays a small and an occasional role in preventing some preterm births. This literature review demonstrates that medical interventions aimed at preventing, not just delaying, preterm birth, are not effective at a population level. Providing holistic, antenatal midwifery care for women living in socio-economic disadvantage and/or with an increased risk of preterm birth seems to be a promising strategy to address the negative effects of the social determinants of disease and thus to reduce the rate of preterm births at an individual and a population level.

Nifedipine in the management of preterm labor: a systematic review and metaanalysis

To determine the efficacy and safety of nifedipine as a tocolytic agent in women with preterm labor. A systematic review and metaanalysis of randomized controlled trials. Twenty-six trials (2179 women) were included. Nifedipine was associated with a significant reduction in the risk of delivery within 7 days of initiation of treatment and before 34 weeks' gestation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, and admission to the neonatal intensive care unit when compared with β₂-adrenergic-receptor agonists. There was no difference between nifedipine and magnesium sulfate in tocolytic efficacy. Nifedipine was associated with significantly fewer maternal adverse events than β₂-adrenergic-receptor agonists and magnesium sulfate. Maintenance nifedipine tocolysis was ineffective in prolonging gestation or improving neonatal outcomes when compared with placebo or no treatment. Nifedipine is superior to β₂-adrenergic-receptor agonists and magnesium sulfate for tocolysis in women with preterm labor.

Effects of Maternal Magnesium Sulfate Administration on Intestinal Blood Flow Velocity in Preterm Neonates

Background: Antenatal MgSO₄ administration is used extensively as a tocolytic agent and to treat preeclampsia. Various effects on the fetus and newborn have been reported, and MgSO₄ has well-documented vasoactive effects. Objective: To determine if antenatal MgSO₄ administration affects intestinal blood flow velocity in newborn preterm infants. Methods: Peak, mean and end-diastolic velocities in the superior mesenteric artery were measured on day 1 of life. Maternal medical records were reviewed to identify infants whose mothers had been administered MgSO₄ for preterm labor or preeclampsia within 24 h of delivery. Result: Fifty-six infants were studied: 27 were exposed and 29 were not exposed to antenatal MgSO₄. Mean birth weight (1,371 ± 349 and 1,401 ± 469 g, respectively), gestational age (29.7 ± 2.0 and 30.0 ± 2.9 weeks, respectively) and infant hemodynamic and clinical variables (other than clinical indication for antenatal MgSO₄ administration) were similar between groups. There were no significant differences between the exposed and unexposed groups in intestinal blood flow velocities. For the exposed group, however, there was a significant negative correlation between mean velocity and the number of hours from birth to the time superior mesenteric artery blood flow velocity measurements were made (p = 0.002); there was no correlation for the unexposed group (p = 0.852). Conclusion: Group mean values indicate that antenatal exposure to MgSO₄ does not significantly affect intestinal blood flow velocity in newborn preterm infants. However, the significant negative relationship between mean blood flow velocity and time from birth to blood flow velocity measurement in exposed infants suggests that there may be measurable effects of MgSO₄ exposure within the hours immediately after birth. Trials that prospectively evaluate the development of intestinal blood flow velocities are needed to further clarify potential effects of antenatal MgSO₄ on the gastrointestinal tract of preterm infants.

Sequential cervical cerclage in the same pregnancy: two multifetal pregnancy case reports

SUMMARY The common availability of assisted reproductive techniques (ART) has brought the increase of multiple pregnancies. Usually, soon after the preterm delivery of the first fetus in multiple pregnancies, the delivery of the remaining fetus also happens. Delayed interval delivery of the remaining fetus after preterm delivery of the first one allows to gain time for fetal lung maturity and to cope with prematurity. We present here live healthy neonatal outcomes in two sequential cases, one twin and one triplet pregnancies, after emergency cerclage followed by second emergency cerclage due to cervical tear with a delayed delivery of 72 and 74 days respectively. The success of pregnancy prolongation in cervical cerclage cases depends on how effectively uterine contractions are prevented and how possible subclinical infections are controlled. We suggest that use of antibiotics, anti-inflammatory and tocolytic agents should be the main target to safely postpone delivery of the remaining twin.

Atosiban in the Management of Preterm Labour

The purpose of this review was to look at the evidence available for the use of atosiban as a tocolytic in cases of threatened preterm labour. A Royal College of Obstetricians and Gynaecologists Green Top Guideline concluded that there was no clear evidence to show a benefit to tocolysis in reducing perinatal and neonatal morbidity and mortality. Using a systematic literature search, we summarise the evidence available on the use of atosiban for the prevention of preterm birth and compare it with other commonly used tocolytic agents in terms of efficacy, patient preference and drug safety. We conclude that although atosiban appears to be the tocolytic of choice, a clear benefit of using tocolysis in all cases of threatened preterm labour remains to be justified and clinical management should be tailored according to individual needs.

The Oxytocin-Oxytocin Receptor System and Its Antagonists as Tocolytic Agents

Oxytocin, a hormone involved in numerous physiologic processes, plays a central role in the mechanisms of parturition and lactation. It acts through its receptor, which belongs to the G-protein-coupled receptor superfamily, while Gq/phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3) is the main pathway via which it exerts its action in the myometrium. Changes in receptor levels, receptor desensitization, and locally produced oxytocin are factors that influence the effect of oxytocin on uterine contractility in labor. Activation of oxytocin receptor causes myometrial contractions by increasing intracellular Ca+2 and production of prostaglandins. Since oxytocin induces contractions, the inhibition of its action has been a target in the management of preterm labor. Atosiban is today the only oxytocin receptor antagonist that is available as a tocolytic. However, the quest for oxytocin receptor antagonists with a better pharmacological profile has led to the synthesis of peptide and nonpeptide molecules such as barusiban, retosiban, L-368,899, and SSR-126768A. Many of these oxytocin receptor antagonists are used only as pharmacological tools, while others have tocolytic action. In this paper, we summarize the action of oxytocin and its receptor and we present an overview of the clinical and experimental data of oxytocin antagonists and their tocolytic action.