Oxytocin receptor antagonists for inhibiting preterm labour

Flenady, Vicki; Reinebrant, Hanna E.; Liley, Helen; Tambimuttu, E. G.; Cole, S.; Papatsonis, Dimitri

doi:10.1002/14651858.cd004452

Cited by 25 publications

(30 citation statements)

References 20 publications

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“…SAR150640 was even more effective than the oxytocin/ vasopressin V 1 a receptor antagonist atosiban, which had only a slight inhibitory effect. In fact atosiban is not better than ␤ 2 -mimetics or placebo in terms of tocolytic efficacy or infant outcomes (Papatsonis et al, 2005). These in vivo results confirm the myorelaxant action of SAR150640 observed in vitro, and they suggest that selective ␤ 3 -adrenoceptor agonists might be more effective and safer than the currently used ␤ 2 -mimetics and oxytocin antagonists to delay delivery in women with premature labor.…”

Section: Discussionsupporting

confidence: 57%

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor

Croci¹,

Cecchi²,

Marini³

et al. 2007

J Pharmacol Exp Ther

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Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino] phenoxy}propyl) amino]cyclohexyl}benzoate hydrochloride (SAR150640) was characterized as a new potent and selective ␤ 3 -adrenoceptor agonist for the treatment of preterm labor. SAR150640 and its major metabolite, the corresponding acid 4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl) amino] phenoxy}propyl)amino]cyclohexyl}benzoic acid (SSR500400), showed high affinity for ␤ 3 -adrenoceptors (K i ϭ 73 and 358 nM) and greater potency than (Ϫ)-isoproterenol in increasing cAMP production in membrane preparations from human neuroblastoma cells (SKNMC), which express native ␤ 3 -adrenoceptors (pEC 50 ϭ 6.5, 6.2, and 5.1, respectively). SAR150640 and SSR500400 also increased cAMP production in membrane preparations from human uterine smooth muscle cells (UtSMC), which also express native ␤ 3 -adrenoceptors (pEC 50 ϭ 7.7 and 7.7, respectively). In these cells, SAR150640 dose-dependently inhibited oxytocin-induced intracellular Ca 2ϩ mobilization and extracellular signal-regulated kinase 1/2 phosphorylation. SAR150640 and SSR500400 had no ␤ 1 -or ␤ 2 -agonist or antagonist activity in guinea pig atrium and trachea, or in human isolated atrium and bronchus preparations. Both compounds concentration-dependently inhibited spontaneous contractions in human near-term myometrial strips, with greater potency than salbutamol and 4-[3-[(1,1-dimethylethyl)-amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP12177) (pIC 50 ϭ 6.4, 6.8, 5.9, and 5.8, respectively), but with similar potency to (Ϫ)-isoproterenol and atosiban (oxytocin/vasopressin V 1 a receptor antagonist). SAR150640 also inhibited the contractions induced by oxytocin and prostaglandin F 2␣ . In vivo, after intravenous administration, SAR150640 (1and 6 mg/kg), but not atosiban (6 mg/kg), dosedependently inhibited myometrial contractions in conscious unrestrained female cynomolgus monkeys, with no significant effects on heart rate or blood pressure. In contrast, salbutamol (50 and 250 g/kg) had no inhibitory effect on uterine contractions, but it dose-dependently increased heart rate. These findings indicate a potential for the therapeutic use of SAR150640 in mammals during preterm labor.Premature labor and its consequence, preterm delivery, defined by the World Health Organization as gestational age at birth of less than 37 complete gestational weeks, are major Article, publication date, and citation information can be found at

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Section: Discussionsupporting

confidence: 57%

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor

Croci¹,

Cecchi²,

Marini³

et al. 2007

J Pharmacol Exp Ther

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“…In Afifa study with nitroglycerin patch, mean prolongation was 2 days. 9,10 In our study when cervical dilatation was 3 cm, mean prolongation of pregnancy with nifedipine was 3.2 days and with nitroglycerin was 2.8 days.…”

Section: Discussionmentioning

confidence: 49%

Transdermal Nitroglycerin Versus Oral Nifedipine Administration for Tocolysis in Preterm Labour

Balasubramani¹,

Kamatchi²

2017

jemds

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BACKGROUND Preterm labour is defined by the world health organization as the onset of labour in a pregnancy before the completion of 37 weeks of gestation and after 20 weeks of gestation. In about 45 -50% of cases of preterm labour, the aetiology remains obscure. So attempts at prevention have not been very encouraging, but arrest of preterm labour continues to be the need of the hour. Currently, main goal for use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating foetal lung maturity and maternal transfer to a tertiary care centre and thereby reducing neonatal morbidity and mortality. There are many number of tocolytic drugs, but unfortunately none has been completely effective because of questionable efficacy and potentially serious side effects outweigh the use of many tocolytic agents.In this study, comparison of effectiveness of oral nifedipine with transdermal nitroglycerin in the inhibition of preterm delivery is being done. MATERIALS AND METHODSStudy on tocolysis in preterm labour was conducted in Government Rajaji Hospital from December 2010 to November 2011; 100 women with preterm labour randomly selected from the pregnant women attending antenatal OP and from labour ward from the Department of Obstetrics and Gynaecology, Government Rajaji Hospital, Madurai. Out of which 50 women were recruited for oral nifedipine and another 50 women were recruited for transdermal nitroglycerin patch. If and time needed for tocolysis, prolongation of pregnancy and the neonatal outcomes were observed. The results were tabulated in performed proforma and meticulously analysed. RESULTSThe study was designed with a total sample of non-randomly selected 100 women who were in preterm labour, out of which 50 women were allotted for oral nifedipine in Group I and another 50 women were non-randomly selected for transdermal nitroglycerin patch in Group II. The age distribution of the two groups has no significant difference. The maximum number of patients in both groups fall in age group between 20 -24 years. There is no significant difference in the antenatal care received, parity, distribution of the presenting part and cervical effacement by the 2 groups of patients. Pre-term labour in previous pregnancy was 22% (11 out of 50) in Group I and 18% (9 out of 50) in Group II. There is no significant difference in the history of pre-term labour between the 2 groups of patients. Though there was not much significant difference in the gestational age on admission in both groups, the time of prolongation of pregnancy varied considerably in both groups. Mean prolongation with Group I was significant when compared to Group II, in case of cervical dilatation 1 cm or less than 1 cm. Time needed for Tocolysis ranging between 2 -12 hours in both the groups. There is significant difference in the incidence of complications among the 2 groups of patients. Among Group I, it was about 6% and in Group II 22%. When the gestational age at delivery was compared in both the groups, it dif...

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“…[35][36][37] For atosiban, no significant fall in DBP occurred, which is consistent with earlier work. [3,32,38,39] …”

Section: Sphygmomanometer Blood Pressurementioning

confidence: 99%

Different effects of tocolytic medication on blood pressure and blood pressure amplification

Fabry¹,

Paepe

Kips

et al. 2010

Eur J Clin Pharmacol

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Oxytocin receptor antagonists for inhibiting preterm labour

Cited by 25 publications

References 20 publications

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor

Transdermal Nitroglycerin Versus Oral Nifedipine Administration for Tocolysis in Preterm Labour

Different effects of tocolytic medication on blood pressure and blood pressure amplification

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Oxytocin receptor antagonists for inhibiting preterm labour

Cited by 25 publications

References 20 publications

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β3-Adrenoceptor Agonist for the Treatment of Preterm Labor

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β3-Adrenoceptor Agonist for the Treatment of Preterm Labor

Transdermal Nitroglycerin Versus Oral Nifedipine Administration for Tocolysis in Preterm Labour

Different effects of tocolytic medication on blood pressure and blood pressure amplification

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Product

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In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β₃-Adrenoceptor Agonist for the Treatment of Preterm Labor