Tocolytic treatment for the management of preterm labor: A review of the evidence

Berkman, Nancy D; Thorp, John M.; Lohr, Kathleen N; Carey, Timothy S.; Hartmann, Katherine E.; Gavin, Norma I.; Hasselblad, Victor; Idicula, Anjolie E.

doi:10.1067/mob.2003.356

Cited by 156 publications

(97 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, b-mimetics are known to be responsible for serious foetal and maternal side effects. For these different reasons, the use of b-mimetics as tocolytic agents has been repeatedly questioned (The Canadian Preterm Labor Investigators Group, 1992;Berkman et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

Rouget

Breuiller-Fouché

Mercier

et al. 2004

British J Pharmacology

View full text Add to dashboard Cite

1 In order to compare the b 2 -and b 3 -adrenoceptor (b-AR) desensitisation process in human nearterm myometrium, we examined the influence of a pretreatment of myometrial strips with either a b 2 -or a b 3 -AR agonist (salbutamol or SR 59119A, respectively, both at 10 mM, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2 To assess some of the mechanisms potentially implicated in the b-AR desensitisation process, we studied the influence of such treatment on the number of b 2 -and b 3 -AR binding sites, the b 2 -and b 3 -AR transcripts expression and the phosphodiesterase 4 (PDE4) activity. 3 Salbutamol, but not SR 59119A, concentration-response curve (CRC) was shifted by a 15 h salbutamol preincubation, with a significant difference in Àlog EC 20 values (6.3170.13 vs 5.5870.24, for control and 15 h salbutamol pretreatment, respectively, Po0.05). Neither salbutamol nor SR 59119A CRCs were modified after a 15 h preincubation with SR 59119A. 4 A 15 h exposure of myometrial strips to salbutamol significantly reduced the salbutamol-induced (0.6070.26 vs 1.5470.24 pmol mg À1 protein, Po0.05), but not the SR 59119A-induced, cAMP production. No decrease in cAMP production was observed after a 15 h SR 59119A exposure. 5 A 15 h salbutamol exposure of myometrial strips significantly reduced the b 2 -but not the b 3 -AR binding site density, whereas no decrease in the number of b 2 -and b 3 -AR binding sites was observed after a 15 h SR 59119A treatment. 6 Neither PDE4 activity nor the b 2 -and b 3 -AR mRNA expression levels were affected by salbutamol or SR 59119A treatments. 7 Our results indicate that b 3 -AR, but not b 2 -AR, are resistant to the agonist-induced desensitisation. In our model, b 2 -AR desensitisation is mediated by a decreased number of b 2 -AR that was not explained by transcriptional regulation of the receptor.

show abstract

Section: Introductionmentioning

confidence: 99%

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

Rouget

Breuiller-Fouché

Mercier

et al. 2004

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…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 causes of morbidity and mortality in infancy (Berkman et al, 2003). Approximately 6 to 12% of all pregnancies end prematurely in Western countries, and deaths of premature babies account for approximately 85% of all perinatal mortality (Goldenberg and Rouse, 1998;Ananth et al, 2001).…”

mentioning

confidence: 99%

“…Unfortunately, available therapies are not altogether effective (Slattery and Morrison, 2002). Current tocolytic therapies include licensed compounds such as ␤ 2 -adrenoceptor agonists (e.g., salbutamol and ritodrine) and the oxytocin/vasopressin V 1 a receptor antagonist atosiban in Europe, as well as several compounds not licensed for this indication but used as off-label treatment, e.g., calcium channel blockers, magnesium sulfate (used in North America), and nonsteroidal anti-inflammatory agents (Berkman et al, 2003). However, they all fail to improve perinatal outcomes, and they often have important side effects, notably cardiovascular, on the mother and/or the fetus.…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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

show abstract

“…calcium channel blockers, oxytocin antagonists, non-steroidal anti-inflammatory agents and magnesium). On the other hand, no significantly better group of agents has yet been found for tocolysis than b 2 -agonists (Berkman et al 2003), although the side effects of the oxytocin antagonist atosiban seem more favorable than that of b 2 -agonists (Moutquin et al 2000, Worldwide Atosiban versus Beta-agonists Study Group 2001.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

et al. 2005

View full text Add to dashboard Cite

The effectiveness of b 2 -agonists in preterm delivery is reduced by several factors. The aim of this study was to determine the influence of late pregnancy in the uterus-relaxing effect of terbutaline in the rat in vitro. Rat uterine tissues from late pregnancy (days 15, 18, 20 and 22) were used. In vitro electrical field-stimulation (EFS) was used to evoke contractions. The radioligand-binding technique, reverse transcription-polymerase chain reaction and radioimmunoassay technique were used to determine the b-adrenergic receptor density and mRNA level and the plasma sex hormone level, respectively. The activated G-protein level of the b-adrenergic receptors was investigated by a radiolabelled GTP binding assay. EFS-induced contractions were inhibited by terbutaline. This effect decreased towards term with respect to both the EC 50 and maximal inhibition values. A drop in plasma progesterone level was also detected. Binding studies revealed an increase in b-adrenergic receptor number on the last day of pregnancy, which correlated with the change in receptor mRNA level. The G-protein-activating effect of terbutaline decreased continuously between days 15 and 20. Surprisingly, terbutaline decreased the G-protein activation to below the basal level on day 22. However, progesterone pretreatment set back the uterine action of terbutaline, increased the density of the b 2 -adrenergic receptors and their mRNA level and increased the G-proteinactivating property of terbutaline. These data provide evidence of a pregnancy-induced decrease in activated G-protein level after b 2 -agonist stimulation. The decrease in plasma progesterone level has a crucial role in this process. The effects of b 2 -adrenergic receptor agonists in tocolytic therapy may possibly be potentiated with progesterone.

show abstract

Tocolytic treatment for the management of preterm labor: A review of the evidence

Cited by 156 publications

References 59 publications

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

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

Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

Contact Info

Product

Resources

About

Tocolytic treatment for the management of preterm labor: A review of the evidence

Cited by 156 publications

References 59 publications

The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

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

Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

Contact Info

Product

Resources

About

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

The human near‐term myometrial β₃‐adrenoceptor but not the β₂‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

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