Effects of oxytocin receptor antagonist atosiban on pregnant myometrium in vitro

Büscher, Ulrich; Chen, Frank C.-K.; Riesenkampff, Eugénie; Dehn, Donata von; David, Matthias; Dudenhausen, Joachim W.

doi:10.1016/s0029-7844(01)01405-3

Cited by 9 publications

(8 citation statements)

References 13 publications

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“…[6] Pregnant women with chronic hypertension have an increased risk of preeclampsia (21–25%), premature delivery (33–35%), intrauterine growth retardation (IUGR)(10–15%), placental abruption (1–3%), and perinatal mortality (4.5%). [31] Of 97 hypertensive patients, perinatal death and low birth weight occurred in 37.5% and 66.60% of deliveries, respectively, and live birth was seen in 62.5% of cases in our study. [6] Thus, hypertension during pregnancy is associated with adverse fetal outcomes and carries maternal mortality rate of 5.5%.…”

Section: Hypertensive Disorders Of Pregnancymentioning

confidence: 60%

The kidney in pregnancy: A journey of three decades

Prakash

2012

Indian J Nephrol

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The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3–5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy.

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Section: Hypertensive Disorders Of Pregnancymentioning

confidence: 60%

The kidney in pregnancy: A journey of three decades

Prakash

2012

Indian J Nephrol

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“…Atosiban is a well-established OTR-A which is approved in Europe. Although the efficacy of atosiban in clinical trials is disputed 27 , it has been repeatedly shown to successfully inhibit OT-induced myometrial contractions in vitro 28–30 by inhibiting inositol triphosphate (IP 3 ) production with decrease in intracellular calcium mobilisation in the myometrial cell 12 as we have shown in this study. Nolasiban is a non-peptide OTR-A, which has a higher selectivity for OTR than V1a receptors when compared to atosiban 14 .…”

Section: Discussionmentioning

confidence: 53%

Oxytocin Receptor Antagonists, Atosiban and Nolasiban, Inhibit Prostaglandin F2α-induced Contractions and Inflammatory Responses in Human Myometrium

Kim

Riaposova

Ahmed

et al. 2019

Sci Rep

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Oxytocin receptor antagonists (OTR-A) have been developed as tocolytics for the management of preterm labour due to the significant role of oxytocin (OT) in the onset of both term and preterm labour. Similar to OT, prostaglandins (PGs) play key roles in myometrial contractility and cervical ripening. Inhibition of PG synthesis/activity is used to delay preterm birth. Thus, targeting the PG pathway in combination with an OTR-A may be an effective strategy for delaying preterm delivery. In this study, we examined the effects of atosiban and nolasiban on PGF 2α -induced contractions and pro-inflammatory responses in human pregnant myometrium. Both OTR-As, atosiban and nolasiban, inhibited PGF 2α -induced contractions in a dose-dependent manner ( p < 0.001 and p < 0.01, res p ectively). These inhibitory effects involved the suppression of PGF 2α -mediated increase in intracellular calcium levels. In addition, the OTR-As significantly suppressed PGF 2α -induced activation of pro-inflammatory pathways such as NF-κB and mitogen activated protein kinases (MAPKs), and the subsequent expression of contraction-associated-protein, COX-2. We have demonstrated that atosiban and nolasiban not only inhibit contractions elicited by OT, but also inhibit contractions and inflammation induced by PGF 2α . This suggests a possible crosstalk between OTR and PG receptor signalling and highlights the importance of understanding G protein-coupled receptor interactions/crosstalk in the development of future tocolytics.

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“…These + ions play an important role in smooth-muscle cell contractions, as the depolarization phase is mainly due to inward currents of Ca 2+ and Na + ions (10,13,14). Since Atosiban blocks the oxytocin receptors impairing the entrance of Ca 2+ ions, it reduces cell excitability, as reported in some in vitro studies on human myometrial cells (12). ).…”

Section: Preterm Labor and Tocolytic Treatmentmentioning

confidence: 93%

“…Specifically, oxytocin molecules have proven to be a key factor in the progression or induction of labor, being capable of increasing uterine activity in humans (10,11). In this sense, Atosiban is a synthetic peptide (desamino-oxytocin analog) that has been shown to be a competitive oxytocin and vasopressin antagonist (11,12). Atosiban, widely used in Europe (9,12), blocks the oxytocin receptors of myometrial cells, inhibiting the release of Ca 2+ ions into the cytoplasm (9).…”

Section: Preterm Labor and Tocolytic Treatmentmentioning

confidence: 99%

“…In this sense, Atosiban is a synthetic peptide (desamino-oxytocin analog) that has been shown to be a competitive oxytocin and vasopressin antagonist (11,12). Atosiban, widely used in Europe (9,12), blocks the oxytocin receptors of myometrial cells, inhibiting the release of Ca 2+ ions into the cytoplasm (9). These + ions play an important role in smooth-muscle cell contractions, as the depolarization phase is mainly due to inward currents of Ca 2+ and Na + ions (10,13,14).…”

Section: Preterm Labor and Tocolytic Treatmentmentioning

confidence: 99%

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Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor

Mas-Cabo

Prats-Boluda

Ye-Lin

et al. 2019

Biomedical Signal Processing and Control

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Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p <0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios.

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Effects of oxytocin receptor antagonist atosiban on pregnant myometrium in vitro

Abstract: The oxytocin receptor antagonist atosiban showed a significant, dose-dependent inhibition of oxytocin-induced contractions of human myometrium in vitro. It might be effective in tocolysis at term.

Cited by 9 publications

References 13 publications

The kidney in pregnancy: A journey of three decades

The kidney in pregnancy: A journey of three decades

Oxytocin Receptor Antagonists, Atosiban and Nolasiban, Inhibit Prostaglandin F2α-induced Contractions and Inflammatory Responses in Human Myometrium

Characterization of the effects of Atosiban on uterine electromyograms recorded in women with threatened preterm labor

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