Atosiban is a mixed antagonist of oxytocin and vasopressin receptors. It effectively inhibits uterine contractions and prolongs pregnancy by competitively blocking oxytocin receptors on uterine smooth muscle[1, 2]. Atosiban is a synthetic peptide tocolytic agent that can be used to treat premature labor[3].
In vitro, treatment of human myometrial cells with Atosiban (10μM) significantly reduced oxytocin (OT)-induced intracellular p38 kinase activation and COX-2 upregulation[4]. Treatment of human umbilical vein endothelial cells (HUVECs) with Atosiban (10μM) significantly inhibited the promoter activity of hypoxia-inducible factor-1 α (HIF-1α) in HUVECs and reduced the mRNA and protein expression of HIF-1α[5].
In vivo, treatment of experimental endometriosis rats with Atosiban (0.5mg/kg/day) by intraperitoneal injection for 21 days significantly reduced the volume of endometriotic implants and significantly reduced the expression level of proliferating cell nuclear antigen in implanted tissues[6]. Treatment of pregnant rats with Atosiban (6mg/kg/day) by intraperitoneal injection for 21 days significantly increased the level of oxidative stress in the plasma and heart tissue of newborn rats[7].
References:
[1] McCafferty G P, Pullen M A, Wu C, et al. Use of a novel and highly selective oxytocin receptor antagonist to characterize uterine contractions in the rat[J]. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007, 293(1): R299-R305.
[2] Kuć P, Laudański P, Pierzyński P, et al. The effect of combined tocolysis on in vitro uterine contractility in preterm labour[J]. Advances in medical sciences, 2011, 56(1): 88-94.
[3] Di Renzo G C. Safety and efficacy of new drugs in preterm labor[J]. Expert Review of Obstetrics & Gynecology, 2007, 2(1): 19-24.
[4] Kim S H, Pohl O, Chollet A, et al. Differential effects of oxytocin receptor antagonists, Atosiban and Nolasiban, on oxytocin receptor–mediated signaling in human amnion and myometrium[J]. Molecular Pharmacology, 2017, 91(4): 403-415.
[5] Zhu J, Wang H, Zhang X, et al. Regulation of angiogenic behaviors by oxytocin receptor through Gli1-indcued transcription of HIF-1α in human umbilical vein endothelial cells[J]. Biomedicine & Pharmacotherapy, 2017, 90: 928-934.
[6] Simsek Y, Celik O, Karaer A, et al. Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis[J]. Archives of gynecology and obstetrics, 2012, 286(3): 777-783.
[7] Simsek Y, Celik O, Karaer A, et al. Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban[J]. Archives of gynecology and obstetrics, 2012, 285(3): 655-661.
Atosiban是一种催产素和加压素受体的混合拮抗剂，通过竞争性阻断子宫平滑肌上的催产素受体，有效抑制宫缩，延长妊娠时间[1, 2]。Atosiban是一种合成的肽类宫缩抑制剂，能够用于治疗早产[3]。
在体外，Atosiban（10μM）处理人子宫肌层细胞，显著降低了催产素（OT）诱导的细胞内p38激酶活化和COX-2的上调[4]。Atosiban（10μM）处理人脐静脉内皮细胞（HUVECs），显著抑制了HUVECs中缺氧诱导因子-1 α（HIF-1α）的启动子活性，降低了HIF-1α的mRNA和蛋白表达[5]。
在体内，Atosiban（0.5mg/kg/day）通过腹腔注射治疗实验性子宫内膜异位症大鼠21天，显著减小了子宫内膜异位症植入物的体积，显著降低了植入组织的增殖细胞核抗原表达水平[6]。Atosiban（6mg/kg/day）通过腹腔注射处理妊娠大鼠21天，显著升高了新生鼠仔血浆和心脏组织的氧化应激水平[7]。