Preterm labour

Relcovaptan (SR-49059) is a selective, orally active V1aR antagonist that prevents pain of primary dysmenorrhea and inhibits preterm labour and could be useful in the treatment of Raynaud s phenomenon. The selective ViBR antagonist SSR149415 showed beneficial effects in the treatment of depression and anxiety in several animal models. 

Barusiban is a long-acting, selective antagonist of OTR that is in development for preterm labour. It has a 300-fold higher affinity for the OTR than for the Vi AR and hence more selective action than atosiban on myometrial tissues. The duration of action may be longer then that of atosiban, providing the convenience... 

Oxytocin Antagonists as Potential Therapeutic Agents for the Treatment of Preterm Labour... 

TREATMENT OF PRETERM LABOUR The Role of Oxytocin in Labour Regulation of Oxytocin during Labour Regulation of the Oxytocin Receptor Experiences with Oxytocin Antagonists Selective OT or Mixed OT/Via Blockade ... 

The only drug that has been lieensed for the treatment of preterm labour in the US is ritodrine, a /1-2 adrenoceptor agonist. -2 Adrenoceptors are... 

More recently, a novel form of therapy in the form of oxytocin antagonists has become available. Though currently only an intravenous formulation for acute therapy is available in Europe (but not in the US), this class of drugs offers hope for a more effective treatment for preterm labour. 

Nearly all the clinical data comes from the use of atosiban (see Peptide Antagonists), a peptide oxytocin antagonist that is licensed in Europe for acute (48 h) treatment of preterm labour. Early clinical studies demonstrated the ability of atosiban to inhibit uterine contractions associated with labour [14]. Following these successful phase II trials, full phase III trials were... 

One compound from this series, (10), has been tested in vitro in human myometrium tissue obtained at term following caesarean section and shown to inhibit contractions induced by oxytocin [44] with a pA2 of 7.6. This is one of the first direct indications that the use of an oxytocin antagonist may be of benefit in the treatment of preterm labour in humans. This compound has been extensively studied in the near-term baboon and has been shown to inhibit nocturnal and near-term contractions following an intravenous bolus injection [45]. Further studies on the effect of oxytocin antagonism in the weeks leading up to delivery in the baboon have also been published [46]. 

Preterm labour is the major cause of perinatal morbidity and mortality. Oxytocin antagonists offer an attractive approach to prevention. Chapter 7 reviews three decades of medicinal chemistry in this field. The peptide approach has resulted in valuable injectable products. Selectivity over the related vasopressin receptors and improvement in pharmacokinetic profile have been the key challenges for more recent non-peptide programmes, and these seem likely to yield orally available medicines. 

Young I have a specific example about a clinical area I know about, which is preterm labour. I have treated patients with pre-term labour, and here we know that... 

A recent Cochrane review failed to demonstrate the advantage of oxytocin receptor antagonists for women with preterm labour as a form of tocolytic therapy. Possible side effects are nausea, vomiting and headache in the mother. Oxytocin receptor antagonists for preterm labour do not improve infant outcomes more than placebo or other tocolytics. 

Papatsonis D, Flenady V, Cole S, LUey H. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev 2005. Issue 3. 

Preterm labour (to mother) to enhance fetal lung maturation. 

Hendricks SK, Smith JR, Moore DE, Brown ZA. Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour. Br J Obstet Gynaecol 1990 97(4) 312-16. 

Lees CC, Lojacono A, Thompson C, Danti L, Black RS, Tanzi P, White IR, Campbell S. Glyceryl trinitrate and ritodrine in tocolysis an international multicenter randomized study. GTN Preterm Labour Investigation Group. Obstet Gynecol 1999 94(3) 403-8. 

Keirse MJNC. Indomethacin tocolysis in preterm labour. In Cochrane Library. CDROM and online versions. 

Leung TN, Zhang J, Lau TK, Hjehn NM, Lo YMD. Maternal plasma fetal DNA as a marker for preterm labour. Lancet 1998 352 1904-5. 

Gaiser RR, Seem EH. Use of rocuronium in a pr nant patient with an open eye injury, receiving magnesium medicati( i, for preterm labour. BrJAnaes 996) 77,669-71. 

Two patients were hospitalized because of preterm labour and were given i.v. ritodrine. The nadir of neu-trocytes was 199/mm and 13/mm in the two cases, respectively. The total dose of ritodrine hydrochloride was calculated to be 7800 mg for 26 days and 2500 mg for 22 days, respectively. The total doses were heavier and administration duration was longer in Case 1, which... 

In human medicine, isoxsuprine has been used for the treatment of Raynaud s phenomenon. However, its major use has been as a tocolytic agent and for the prevention of preterm labour. It has also been used in the treatment of cardiovascular disease. Unfortunately, the use of isoxsuprine... 

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