阿托西班通过催产素阻止子宫肌层释放 IP3。子宫肌层细胞骶浆网释放的细胞内钙和通过电压门控通道的外部 Ca2+ 流入均减少。此外，当催产素存在时，阿托西班可以阻止蜕膜释放 PGE 和 PGF [1]。

阿托西班影响精氨酸加压素对胎儿-母体心血管和肾脏系统的生理作用。垂体后叶激素催产素和精氨酸加压素在结构上仅存在两个氨基酸的差异。一项使用阿托西班一小时的试验并未对妊娠晚期绵羊的母亲或胎儿的心血管系统造成任何变化[1]。在小鼠的臂旁核中，阿托西班抑制表达催产素受体的神经元的激活[2]。

Absorption, Distribution and Excretion
In women receiving 300 μg/min by infusion for 6-12 h, average steady state concentrations of 442 ng/mL were reached within 1 h. Steady state concentrations increase proportionally to dosage.
Small amounts of atosiban are found in the urine with 50 times the amount appearing as the large fragment metabolite (des-(Orn⁸, Gly⁹-NH2)-[Mpa¹, D-Tyr(Et)², Thr⁴]-oxytocin. The amount of drug excreted in the feces is not known.
Atosiban has a mean volume of distribution of 41.8 L. Atosiban crosses the placenta and, at a dose of 300 μg/min, was found to have a 0.12 maternal/fetal concentration ratio.
Atosiban has a mean clearance rate of 41.8 L/h.

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Metabolism / Metabolites
There are two metabolites of atosiban created through the cleavage of the peptide bond between ornithine and proline which is thought to be facilitated by prior cleavage of the disulfide bridge. The larger fragment remains active as an antagonist of oxytocin receptors but is 10 times less potent than the parent molecule. At a dosage of 300 μg/min the ratio of parent molecule to the main metabolite was observed to be 1.4 at the second hour and 2.8 at the end of infusion.

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Biological Half-Life
Atosiban does not conform to either 1-compartment or 2-compartment kinetics. It has been determined to have an initial half life (tα) of 0.21 h and a terminal half life (tβ) of 1.7 h.

Protein Binding
Atosiban is 46-48% bound to plasma proteins in pregnant women. It is not known to partition into red blood cells. Differences in the free fraction of drug between maternal and fetal compartments are unknown.

[1]. Sanu O, et al. Critical appraisal and clinical utility of atosiban in the management of preterm labor. Ther Clin Risk Manag. 2010 Apr 26;6:191-9.
[2]. Philip J Ryan, et al. Oxytocin-receptor-expressing Neurons in the Parabrachial Nucleus Regulate Fluid Intake. Nat Neurosci. 2017 Dec;20(12):1722-1733.

Atosiban is an oligopeptide.
Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used intravenously to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form. Atobisan was developed by the Swedish company Ferring Pharmaceuticals. It was first reported in the literature in 1985. Atosiban is licensed in proprietary and generic forms for the delay of imminent pre-term birth in pregnant adult women.

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Drug Indication
Atosiban is indicated for use in delaying imminent pre-term birth in pregnant adult women with: - regular uterine contractions of at least 30 s duration at a rate of at least 4 per 30 min - a cervical dilation of 1-3cm (0-3cm for nulliparas) and effacement of at least 50% - a gestational age of 24-33 weeks - a normal fetal heart rate
Tractotile is indicated to delay imminent pre-term birth in pregnant adult women with: regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes; a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50%; a gestational age from 24 until 33 completed weeks; a normal foetal heart rate.
Atosiban is indicated to delay imminent pre-term birth in pregnant adult women with: regular uterine contractions of at least 30 seconds' duration at a rate of ≥ 4 per 30 minutes; a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50%; a gestational age from 24 until 33 completed weeks; a normal foetal heart rate.

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Mechanism of Action
Atosiban is a synthetic peptide oxytocin antagonist. It resembles oxytocin with has modifications at the 1, 2, 4, and 8 positions. The N-terminus of the cysteine residue is deaminated to form 3-mercaptopropanic acid at position 1, at position 2 L-tyrosine is modified to D-tyrosine with an ethoxy group replacing the phenol , threonine replaces glutamine at postion 4, and ornithine replaces leucine at position 8. It binds to membrane bound oxytocin receptors on the myometrium and prevents oxytocin-stimulated increases in inositol triphosphate production. This ultimately prevents release of stored calcium from the sarcoplasmic reticulum and subsequent opening of voltage gated calcium channels. This shutdown of cytosolic calcium increase prevents contractions of the uterine muscle, reducing the frequency of contractions and inducing uterine quiescence. Atosiban has more recently been found to act as a biased ligand at oxytocin receptors. It acts as an antagonist of Gq coupling, explaining the inhibition of the inositol triphosphate pathway thought to be responsible for the effect on uterine contraction, but acts as an agonist of Gi coupling. This agonism produces a pro-inflammatory effect in the human amnion, activating pro-inflammatory signal tranducer NF-κB. It is thought that this reduces atosiban's effectiveness compared to agents which do not produce inflammation as inflammatory mediators are known to play a role in the induction of labour.

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Pharmacodynamics
Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence.

C43H67N11O12S2

994.19

993.441

90779-69-4

Atosiban acetate;914453-95-5

5311010

Typically exists as solid at room temperature

1.3±0.1 g/cm3

1469.0±65.0 °C at 760 mmHg

842.2±34.3 °C

0.0±0.3 mmHg at 25°C

1.549

-3.41

416.27

11

15

18

68

1770

9

CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSCCC(=O)N[C@@H](C(=O)N1)CC2=CC=C(C=C2)OCC)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCN)C(=O)NCC(=O)N)CC(=O)N)[C@@H](C)O

VWXRQYYUEIYXCZ-OBIMUBPZSA-N

InChI=1S/C43H67N11O12S2/c1-5-23(3)35-41(63)53-36(24(4)55)42(64)50-29(20-32(45)56)38(60)51-30(43(65)54-17-8-10-31(54)40(62)49-27(9-7-16-44)37(59)47-21-33(46)57)22-68-67-18-15-34(58)48-28(39(61)52-35)19-25-11-13-26(14-12-25)66-6-2/h11-14,23-24,27-31,35-36,55H,5-10,15-22,44H2,1-4H3,(H2,45,56)(H2,46,57)(H,47,59)(H,48,58)(H,49,62)(H,50,64)(H,51,60)(H,52,61)(H,53,63)/t23-,24+,27-,28+,29-,30-,31-,35-,36-/m0/s1

(2S)-N-[(2S)-5-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-[(2S)-butan-2-yl]-16-[(4-ethoxyphenyl)methyl]-10-[(1R)-1-hydroxyethyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide

Atosiban RWJ-22164 RW22164 TractocileRWJ22164 RW-22164 TractocileRWJ 22164

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~16.67 mg/mL (~16.77 mM)
DMSO : ≥ 16.67 mg/mL (~16.77 mM)

配方 1 中的溶解度: ≥ 1.67 mg/mL (1.68 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 16.7 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 1.67 mg/mL (1.68 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 16.7mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 1.67 mg/mL (1.68 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 16.7 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。