Evaluation of 1-deamino-[D-Tyr(Oethyl)2, Thr4, Orn8] vasotocin, an oxytocin antagonist in animal models of uterine contractility and preterm labor: A new tocolytic agent

Hahn, Do Won; Demarest, Keith T.; Ericson, Eric; Homm, Roger E.; Capetola, Robert J.; McGuire, J.L.

doi:10.1016/s0002-9378(87)80099-6

Cited by 44 publications

(23 citation statements)

References 4 publications

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“…The similarity of data obtained in this study with those reported for the agonist (Cort et al 1979) and the antagonist (Melin et al 1986, Hahn et al 1987 indicated that the assay was appropriate. Since the extracts were chromatographically purified and only the fractions corresponding to authentic oxytocin standard were assayed, the present data indicated that biologically active oxytocin was present in the tissues examined.…”

Section: Resultssupporting

confidence: 85%

Bioactive oxytocin in human and baboon corpora lutea

Khan-Dawood

Yang²,

Anwer³

et al. 1995

Journal of Endocrinology

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Oxytocin has been identified in both non-human primate and human corpora lutea of the menstrual cycle by RIA, immunocytochemistry and HPLC. Evidence for the transcription of the oxytocin gene in this tissue using PCR is available. Oxytocin receptors have been characterized by biochemical procedures. However, there is some debate as to whether the oxytocin identified in these tissues is biologically active and has a role in luteal function. In this study we have demonstrated that oxytocin isolated by gel chromatography of tissue extracts from the baboon and the human corpus luteum is biologically active as determined in a rat uterine bioassay. Since both oxytocin and its receptors are present in these tissues, it is suggested that oxytocin in the human and non-human primate corpora lutea has a functional role.

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Section: Resultssupporting

confidence: 85%

Bioactive oxytocin in human and baboon corpora lutea

Khan-Dawood

Yang²,

Anwer³

et al. 1995

Journal of Endocrinology

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“…Recently Hahn et al [12] demonstrated that CAP caused a dose-dependent delay of ongoing labour in rats as well as a dose-dependent inhibition of oxytocin-induced contractions in the guinea pig uterus in situ. Corresponding studies on dif ferent oxytocin analogues should be of importance for comparing and evaluating quantitatively the tocolytic effect and which analogue is most useful in clinical trials for treatment of premature labour and dysmenorrhoea.…”

Section: Discussionmentioning

confidence: 99%

Binding of Four Oxytocin Analogues to Myometrial Oxytocin and Arginine-Vasopressin Binding Sites in Pregnant Women

Rydén¹,

Andersson²,

Berg³

et al. 1990

Gynecol Obstet Invest

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The binding of ³H-oxytocin (³H-OT) and ³H-arginine-vasopressin (³H-AVP) and the displacement from binding sites by four oxytocin analogues were studied in myometrial membrane preparations from full-term pregnant women. Specific ³H-OT binding was saturable with a maximal binding capacity of 76.1 fmol/mg DNA, and a dissociation constant of 0.5 pM. Corresponding values regarding ³H-AVP was 148.6 fmol/mg DNA and 0.7 pM. The oxytocin analogues tested demonstrated a high specific binding to the OT and AVP receptor sites; in fact, the affinity of the analogues to the ³H-AVP binding sites was higher than to the ³H-OT binding sites. The order of potency between the analogues was CAU > CAM > CAP > CAO and CAP > CAU > CAO > CAM for the OT and AVP binding sites, respectively. The displacement of oxytocin and arginine-vasopressin, respectively, from the myometrial receptor sites indicate partly separate binding sites for oxytocin and AVP and might implicate that AVP can be of importance in regulating myometrial activity in pregnancy. The results on oxytocin analogues imply that other pharmacological tests must be performed for quantification of the relaxing effects on the uterus and to determine the optimal analogue for clinical trials in preterm labor and dysmenorrhoea.

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“…For a detailed discussion on the clinical trials and the safety profile of atosiban, the reader is referred to section II/4.3. Atosiban (16) was shown to be a highly potent antagonist in vitro [231], as well as in different animal models of uterine hyperactivity [232,233]. The OT/AVP receptor selectivity of atosiban was found to be markedly species dependent, with a much lower OT versus AVP receptor specificity in humans compared to rats and rabbits [234,235].…”

Section: Peptide Antagonistsmentioning

confidence: 99%

Preterm Labour: An Overview of Current and Emerging Therapeutics

Schwarz¹,

Page²

2003

CMC

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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. More recently, a new therapeutic agent, atosiban (Tractocile( trade mark )), a peptidic oxytocin receptor antagonist, has been introduced to the market. However, the use of the various pharmacological agents to treat preterm labour remains restricted, due to lack of uterine selectivity, low efficacy and potentially serious side effects for the mother or the foetus. Therefore, there is an urgent need to develop drugs with myometrial selectivity that would allow long-lasting inhibition of labour and prolong pregnancy up to a stage when good foetal maturation raises the chances of survival. One of the major obstacles hampering the development of new therapeutic agents is the marked inter-species difference in terms of preterm labour physiology, which complicates the preclinical evaluation of new candidate molecules in animal models of disease. In this review, the authors will provide a comprehensive update of past, current and new approaches for the management of preterm labour, including beta(2)-adrenergic agonists, calcium channel blockers, oxytocin antagonists, prostaglandin antagonists and other potential therapeutics. For each of the therapies used today, the review will cover the mechanism of action, benefit and adverse effects, and discuss the promise and potential benefits of new emerging therapeutic agents.

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Evaluation of 1-deamino-[D-Tyr(Oethyl)2, Thr4, Orn8] vasotocin, an oxytocin antagonist in animal models of uterine contractility and preterm labor: A new tocolytic agent

Cited by 44 publications

References 4 publications

Bioactive oxytocin in human and baboon corpora lutea

Bioactive oxytocin in human and baboon corpora lutea

Binding of Four Oxytocin Analogues to Myometrial Oxytocin and Arginine-Vasopressin Binding Sites in Pregnant Women

Preterm Labour: An Overview of Current and Emerging Therapeutics

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