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Eran Hadar, Nir Melamed, Amir Aviram, Oded Raban, Liat Saltzer, Liran Hiersch, Yariv Yogev
OBJECTIVE: The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery. STUDY DESIGN: Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus...
October 2013: American Journal of Obstetrics and Gynecology
Maurice Manning, Stoytcho Stoev, Bice Chini, Thierry Durroux, Bernard Mouillac, Gilles Guillon
Oxytocin (OT) and vasopressin (AVP) mediate their biological actions by acting on four known receptors: The OT (uterine) and the AVP V(1a) (vasopressor), V(1b) (pituitary), V(2) (renal) receptors and a fifth putative AVP V(1c)? (vasodilating) receptor. This presentation will summarize some highlights of the recent progress, in the design and synthesis of selective peptide agonists, antagonists, radioiodinated ligands, fluorescent ligands and bivalent ligands for these receptors. Here we present published and unpublished pharmacological data on the most widely used agonists, antagonists and labelled ligands...
2008: Progress in Brain Research
Torsten M Reinheimer
BACKGROUND: Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin V1A/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored...
2007: BMC Pregnancy and Childbirth
P Husslein, L C Roura, J Dudenhausen, H Helmer, R Frydman, N Rizzo, D Schneider et al.
OBJECTIVE: To evaluate the efficacy and safety of early administration compared with standard administration of atosiban, when predefined eligibility criteria were met. DESIGN: A prospective, open-label, randomised clinical trial. Women were randomised to receive atosiban either immediately (early) or when specified criteria, in terms of duration/frequency of uterine contraction or status of cervical dilation/effacement, were fulfilled (standard). SETTING: Carried out at 105 centres in six European countries...
December 2006: BJOG: An International Journal of Obstetrics and Gynaecology
Maurice Manning, Ling Ling Cheng, Stoytcho Stoev, Nga Ching Wo, W Y Chan, Hazel H Szeto, Thierry Durroux, Bernard Mouillac, Claude Barberis
The peptide oxytocin (OT) antagonist atosiban, approved for tocolytic use in Europe (under the tradename Tractocile), represents an important new therapeutic advance for the treatment of premature labor. This paper presents some new peptide OT antagonists which offer promise as superior tocolytics. The solid phase synthesis is reported of four pairs of L and D-2-naphthylalanine (L/D-2Nal) position-2 modified analogs of the following four oxytocin (OT) antagonists: des-9-glycinamide [1-(beta-mercapto-beta,beta-pentamethylene propionic acid), 2-O-methyltyrosine, 4-threonine]ornithine-vasotocin (desGly-NH(2),d(CH(2))(5)[Tyr(Me)(2),Thr(4)]OVT) (A); the Tyr-NH(2) (9) analog of (A), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2) (9)]OVT (B); the Eda(9) analog of (A), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Eda(9)]OVT (C); and the retro COCH(2)Ph(4-0H)(10) modified analog of (C), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Eda(9)<-- COCH(2)Ph(4-0H)(10)]OVT (D)...
October 2005: Journal of Peptide Science: An Official Publication of the European Peptide Society
Matthias K Schwarz, Patrick Page
Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the US FDA and still remains the standard therapy for treating preterm labour. Ritodrine (Yutopar( trade mark )) stimulates the beta(2)-adrenergic receptor throughout the body, causing an inhibitory action in different tissues that, among other side effects, also leads to an attenuation of uterine contractility...
August 2003: Current Medicinal Chemistry
Hanns Helmer, M Brunbauer, K Rohrmeister
The purpose of this retrospective study is to evaluate the effects of atosiban (Tractocile available in Austria since February 2000) for routine treatment of women with threatened preterm delivery. The advantage of this drug compared to other tocolytic agents is its specific action on reproductive tissues without the accompanying severe side effects. Women (n = 208) were retrospectively evaluated. Diagnoses at admission were preterm labour (n = 117), preterm rupture of membranes (n = 65), incompetent cervix (n = 19) and vaginal bleeding (n = 7)...
April 2003: BJOG: An International Journal of Obstetrics and Gynaecology
P Husslein, J P Quartarolo
A phase IV multinational, multicentre study has been designed--the Tractocile Efficacy Assessment Survey in Europe (TREASURE). The aim is to assess atosiban in the clinical setting, which is associated with fewer restrictions than in phase III trials. Atosiban is to be compared with 'usual care' in women eligible for treatment, and will also be evaluated as deferred or immediate treatment in women who have not yet fulfilled the diagnostic criteria for pre-term labour. Exploring the use of atosiban beyond the normal indications may allow the identification of additional subpopulations of women who will benefit from early treatment...
March 2003: International Journal of Clinical Practice
M Manning, S Stoev, L L Cheng, N C Wo, W Y Chan
We report the solid phase synthesis of four pairs of L- and D-thienylalanine (Thi/D-Thi) position two modified analogues of the following four oxytocin (OT) antagonists: des-9-glycinamide [1-(beta-mercapto-beta,beta-pentamethylene propionic acid), 2-O-methyltyrosine, 4-threonine]ornithine-vasotocin (desGly(NH2)9,d (CH2)5[Tyr(Me)2,Thr4]OVT) (A); the Tyr-(NH2)9 analogue of (A), d(CH2)5[Tyr(Me)2,Thr4,Tyr-(NH2)9]OVT (B); the Eda9 analogue (where Eda = ethylenediamine) of (A), d(CH2)5[Tyr(Me)2, Thr4, Eda9]OVT (C); and the retro Tyr10 modified analogue of (C), d(CH2)5[Tyr(Me)2, Thr4, Eda9<--Tyr10]OVT (D)...
September 2001: Journal of Peptide Science: An Official Publication of the European Peptide Society
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