| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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| 靶点 |
μ-opioid receptor (μOR) with antagonist activity (IC₅₀ = 0.8 nM in radioligand binding assay)
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|---|---|
| 体外研究 (In Vitro) |
1. 受体结合实验:
- 溴化甲基纳曲酮在表达人μOR的CHO细胞膜上显示高亲和力,抑制常数(Kᵢ)为0.7 nM,对μOR的选择性比δ和κ受体高100倍以上
2. GTPγS结合实验: - 抑制μOR介导的G蛋白活化,IC₅₀为1.2 nM,证实拮抗作用 |
| 体内研究 (In Vivo) |
1. 阿片诱导便秘模型:
- 在吗啡诱导的便秘大鼠中,皮下注射溴化甲基纳曲酮(0.3 mg/kg)逆转胃肠道传输延迟而不影响镇痛效果。作用持续6-8小时,给药后2小时达峰
2. 神经保护研究: - 在小鼠缺血性中风模型中,腹腔注射溴化甲基纳曲酮(1 mg/kg)减少35%梗死体积并改善神经功能评分。此效应归因于外周μOR拮抗减少神经炎症 |
| 酶活实验 |
1. 放射性配体结合实验:
- 将表达人μOR的CHO细胞膜与[³H]-二氢吗啡(0.5 nM)及不同浓度的溴化甲基纳曲酮(0.01 nM–10 μM)在Tris-HCl缓冲液(pH 7.4)中25°C孵育60分钟。非特异性结合用1 μM纳洛酮测定。IC₅₀值通过非线性回归计算
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| 细胞实验 |
- cAMP抑制实验:
- 稳定表达μOR的SH-SY5Y细胞经溴化甲基纳曲酮(0.1 nM–10 μM)处理后,用DAMGO(100 nM)刺激。通过酶免疫法检测细胞内cAMP水平。该化合物逆转DAMGO诱导的cAMP抑制,IC₅₀为1.5 nM
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| 动物实验 |
1. Subcutaneous Administration in Rats:
- Methylnaltrexone bromide was formulated in saline and administered subcutaneously at 0.3 mg/kg to rats with morphine-induced constipation. Gastrointestinal transit was measured by charcoal meal assay. Plasma samples were collected at 0, 0.5, 1, 2, 4, 6, and 8 hours post-dose
2. Intraperitoneal Administration in Mice: - For stroke model, Methylnaltrexone bromide (1 mg/kg) was dissolved in sterile saline and administered intraperitoneally 30 minutes after middle cerebral artery occlusion. Neurological deficits were evaluated using a 5-point scale at 24 hours post-ischemia |
| 药代性质 (ADME/PK) |
- Absorption:
- Oral bioavailability in rats was 12%, with peak plasma concentration (Cₘₐₓ) of 25 ng/mL at 1 hour post-dose. Subcutaneous bioavailability was 85%
- Metabolism: - Primarily metabolized by hepatic CYP3A4 to inactive conjugates. Less than 5% of the dose was excreted unchanged in urine - Half-life: - Plasma t½ was 3.5 hours in rats, with prolonged receptor occupancy due to slow dissociation from μOR |
| 毒性/毒理 (Toxicokinetics/TK) |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation No information is available on the use of methylnaltrexone during breastfeeding. The manufacturer recommends avoiding breastfeeding in mothers taking methylnaltrexone. Based on pharmacokinetic data, the oral absorption of methylnaltrexone appears to be very low. Observe breastfed infants who have been exposed to opioids during pregnancy or postpartum for signs of opioid withdrawal, especially diarrhea. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. - Acute Toxicity: - LD₅₀ in mice exceeded 2000 mg/kg (oral), with no signs of organ toxicity in histopathological analysis - Plasma Protein Binding: - 92% bound to plasma proteins in human serum, which may influence distribution and clearance |
| 参考文献 |
[1]. J Cell Physiol. 2021 Nov;236(11):7698-7710. Hyperlink: https://pubmed.ncbi.nlm.nih.gov/34038587/
[2]. Neuropharmacology. 2021 Mar 1;185:108437. Hyperlink: https://pubmed.ncbi.nlm.nih.gov/33316279/ |
| 其他信息 |
- Background:
- Methylnaltrexone bromide is a quaternary amine derivative of naltrexone, designed to minimize blood-brain barrier penetration. It is clinically approved for opioid-induced constipation in patients with advanced illness
- Mechanism: - Competitive antagonist at peripheral μOR, blocking opioid-induced gastrointestinal effects without reversing analgesia. Its long duration of action is attributed to slow off-rate from the receptor - Clinical Potential: - Phase III trials demonstrated safety and efficacy in reducing opioid-induced constipation with minimal systemic side effects. However, cases of gastrointestinal perforation have been reported in patients with advanced illness |
| 分子式 |
C21H26NO4BR
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|---|---|
| 分子量 |
436.33944
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| 精确质量 |
435.105
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| 元素分析 |
C, 57.81; H, 6.01; Br, 18.31; N, 3.21; O, 14.67
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| CAS号 |
73232-52-7
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| PubChem CID |
5361917
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| 外观&性状 |
Typically exists as solid at room temperature
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| 熔点 |
237-239ºC
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| LogP |
3.025
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| tPSA |
69.59
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| 氢键供体(HBD)数目 |
2
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| 氢键受体(HBA)数目 |
5
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| 可旋转键数目(RBC) |
2
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| 重原子数目 |
27
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| 分子复杂度/Complexity |
664
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| 定义原子立体中心数目 |
4
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| SMILES |
C[N+]1(CC[C@@]23C4=C5C=CC(=C4O[C@H]3C(=O)CC[C@]2([C@H]1C5)O)[O-])CC6CC6.Br
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| InChi Key |
IFGIYSGOEZJNBE-KNLJMPJLSA-N
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| InChi Code |
InChI=1S/C21H25NO4.BrH/c1-22(11-12-2-3-12)9-8-20-17-13-4-5-14(23)18(17)26-19(20)15(24)6-7-21(20,25)16(22)10-13;/h4-5,12,16,19,25H,2-3,6-11H2,1H3;1H/t16-,19+,20+,21-,22?;/m1./s1
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| 化学名 |
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-one;bromide
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| 别名 |
MOA-728; MOA728; Methylnaltrexone bromide; Naltrexone methobromide; Relistor; N-Methylnaltrexone Bromide; MRZ-2663BR; bromuro de metilnaltrexona; ...; 73232-52-7; MOA 728
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方,主要用于溶解难溶或不溶于水的产品(水溶度<1 mg/mL)。 建议您先取少量样品进行尝试,如该配方可行,再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80: Saline = 10 : 5 : 85 (如: 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备:将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中,得到澄清溶液。 注射用配方 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (如: 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如: 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液,加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如:100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中,得到0.5%CMC-Na澄清溶液;然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中,得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 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。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2918 mL | 11.4590 mL | 22.9179 mL | |
| 5 mM | 0.4584 mL | 2.2918 mL | 4.5836 mL | |
| 10 mM | 0.2292 mL | 1.1459 mL | 2.2918 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04083651 | WITHDRAWN | Drug: Methylnaltrexone bromide Drug: Placebo |
Pancreatic Cancer | Bausch Health Americas, Inc | 2020-01-06 | Phase 2 Phase 3 |
| NCT01004393 | COMPLETEDWITH RESULTS | Drug: Methylnaltrexone bromide | Constipation Neoplasms Opioid-Related Disorders |
University of Vermont | 2009-10 | Phase 2 |
| NCT00672139 | COMPLETEDWITH RESULTS | Drug: Methylnaltrexone bromide | Opioid-Induced Constipation | Bausch Health Americas, Inc | 2008-07 | Phase 4 |
| NCT04787848 | RECRUITING | Drug: Relistor Injectable Product | Chronic Widespread Pain | University of Alabama at Birmingham | 2021-11-15 | Not Applicable |
| NCT04151719 | WITHDRAWN | Drug: Methylnaltrexone bromide (MNTX) | Pancreatic Cancer | Bausch Health Americas, Inc. | 2020-02-03 | Phase 3 |