| 规格 | 价格 | 库存 | 数量 |
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| 10 mM * 1 mL in DMSO |
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| 10mg |
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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 |
β1 adrenoceptor
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|---|---|
| 体外研究 (In Vitro) |
美托洛尔（0-1000 μg/mL；24-72 小时）对 U937 和 MOLT-4 细胞具有剂量和时间依赖性的细胞毒性作用[3]。细胞毒性测定[3] 细胞系：U937 和 MOLT-4 细胞 浓度：1、10、50、100、500 和 1000 μg/mL 孵育时间：24、48 和 72 小时 结果：显着降低 U937 和 MOLT 的活力-4 细胞在 1000 μg/mL (3740.14μM) 浓度下孵育 48 小时后，显着降低 U937 细胞在 ≥500 μg/ml (≥1870.07μM) 浓度下孵育 72 小时后的活力，并显着降低孵育 72 小时后，MOLT4 细胞浓度≥100 μg/ml (≥374.01μM)。
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| 体内研究 (In Vivo) |
美托洛尔（2.5 mg/kg/h；输注；11 周）可减少 ApoE−/− 小鼠的促炎细胞因子和动脉粥样硬化[1]。美托洛尔（15 mg/kg/q12h；ig；5 天）在柯萨奇病毒 B3 诱导的病毒性心肌炎小鼠模型中显示出抗炎和抗病毒作用[2]。美托洛尔（2.5 mg/kg；静脉注射；3 次推注）显着降低冠状动脉微栓塞 (CME) 大鼠中活化的 caspase-9 蛋白表达并抑制心肌细胞凋亡[4]。动物模型：雄性 ApoE−/− 小鼠[1] 剂量：2.5 mg/kg/h 给药方法：通过微型渗透泵，11 周 结果：胸主动脉动脉粥样硬化斑块面积显着减少，血清 TNFα 和趋化因子 CXCL1 减少，并减少斑块中的巨噬细胞含量。动物模型：Balb/c小鼠，柯萨奇病毒B3（CVB3）诱导的病毒性心肌炎（VMC）模型[2] 剂量：15 mg/kg/q12h 给药方式：口服灌胃，连续5天 结果：CVB3感染引起的VMC病理评分降低，通过降低血清 cTn-I 水平来保护心肌免受病毒损伤。降低心肌促炎细胞因子的水平并增加抗炎细胞因子的表达。心肌病毒滴度显着降低。
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| 细胞实验 |
细胞系：U937 和 MOLT-4 细胞
浓度：1、10、50、100、500 和 1000 μg/mL 孵育时间：24、48 和 72 小时 结果：显着降低细胞活力孵育 48 小时后，MOLT-4 和 U937 细胞浓度为 1000 μg/mL (3740.14μM)；同样，72小时后，观察浓度≥100μg/ml（≥374.01μM）的MOLT4细胞和浓度≥500μg/ml（≥1870.07μM）的U937细胞的活力。 |
| 动物实验 |
Male ApoE-/- mice
2.5 mg/kg/h Via osmotic minipumps, 11 weeks |
| 药代性质 (ADME/PK) |
Absorption
When metoprolol is administered orally, it is almost completely absorbed in the gastrointestinal tract. The maximum serum concentration is achieved 20 min after intravenous administration and 1-2 hours after oral administration. The bioavailability of metoprolol is of 100% when administered intravenously and when administered orally it presents about 50% for the tartrate derivative and 40% for the succinate derivative. The absorption of metoprolol in the form of the tartrate derivative is increased by the concomitant administration of food. Route of Elimination Metoprolol is mainly excreted via the kidneys. From the eliminated dose, less than 5% is recovered unchanged. Volume of Distribution The reported volume of distribution of metoprolol is 4.2 L/kg. Due to the characteristics of metoprolol, this molecule is able to cross the blood-brain barrier and even 78% of the administered drug can be found in cerebrospinal fluid. Clearance The reported clearance rate on patients with normal kidney function is 0.8 L/min. In cirrhotic patients, the clearance rate changes to 0.61 L/min. Plasma levels following oral administration of conventional metoprolol tablets, however, approximate 50% of levels following intravenous adminsitration, indicating about 50% first-pass metabolism... Elimination is mainly by biotransformation in the liver. View More
Metoprolol tartrate is rapidly and almost completely absorbed from the GI tract; absorption of a single oral dose of 20-100 mg is complete in 2.5-3 hours. After an oral dose, about 50% of the drug administered as conventional tablets appears to undergo first-pass metabolism in the liver. Bioavailability of orally administered metoprolol tartrate increases with increased doses, indicating a possible saturable disposition process of low capacity such as tissue binding in the liver. Steady-state oral bioavailability of extended-release tablets of metoprolol succinate given once daily at dosages equivalent to 50-400 mg of metoprolol tartrate is about 77% of that of conventional tablets at corresponding dosages given once daily or in divided doses. Food does not appear to affect bioavailability of metoprolol succinate extended-release tablets. Following a single oral dose as conventional tablets, metoprolol appears in the plasma within 10 minutes and peak plasma concentrations are reached in about 90 minutes. When metoprolol tartrate conventional tablets are administered with food rather than on an empty stomach, peak plasma concentrations are higher and the extent of absorption of the drug is increased. Following oral administration of metoprolol succinate as extended-release tablets, peak plasma metoprolol concentrations are aobut 25-50% of those attained after administration of metoprolol tartrate conventional tablets given once daily or in divided doses. Time to peak concentration is longer with extended-release tablets, with peak plasma coentrations being reached in about 7 hours following administration of such tablets. Plasma concentrations attained 1 hour after an oral dose are linearly related to metoprolol tartrate doses ranging from 50-400 mg as conventional tablets.
Metabolism / Metabolites Metoprolol goes through significant first-pass hepatic metabolism which covers around 50% of the administered dose. The metabolism of metoprolol is mainly driven by the activity of CYP2D6 and to a lesser extent due to the activity of CYP3A4. The metabolism of metoprolol is mainly represented by reactions of hydroxylation and O-demethylation. Metoprolol does not inhibit or enhance its own metabolism. Three main metabolites of the drug are formed by oxidative deamination, O-dealkylation with subsequent oxidation, and aliphatic hydroxylation; these metabolites account for 85% of the total urinary excretion of metabolites. The metabolites apparently do not have appreciable pharmacologic activity. The rate of hydroxylation, resulting in alpha-hydroxymetoprolol, is genetically determined and is subject to considerable interindividual variation. Poor hydroxylators of metoprolol have increased areas under the plasma concentration-time curves, prolonged elimination half-lives (about 7.6 hours), higher urinary concentrations of unchanged drug, and negligible urinary concentrations of alpha-hydroxymetoprolol compared with extensive hydroxylators. Beta-adrenergic blockade of exercise-induced tachycardia persists for at least 24 hours after administration of a single 200-mg oral dose of metoprolol tartrate in poor hydroxylators. Controlled studies have shown that debrisoquine oxidation phenotype is a major determinant of the metabolism, pharmacokinetics and some of the pharmacological actions of metoprolol. The poor metabolizer phenotype is associated with increased plasma drug concentrations, a prolongation of elimination half-life and more intense and sustained beta blockade. Phenotypic differences have also been observed in the pharmacokinetics of the enantiomers of metoprolol. In vivo and in vitro studies have identified some of the metabolic pathways which are subject to the defect, that is alpha-hydroxylation and O-demethylation. PMID:2868819 Metropolol is a racemic mixture of R-and S-enantiomers, and is primarily metabolized by CYP2D6. Biological Half-Life The immediate release formulations of metoprolol present a half-life of about 3-7 hours. The plasma half-life ranges from approximately 3 to 7 hours. |
| 毒性/毒理 (Toxicokinetics/TK) |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Because of the low levels of metoprolol in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. Studies on the use of metoprolol during breastfeeding have found no adverse reactions in breastfed infants. Monitor breastfed infants for symptoms of beta blockade such as bradycardia and listlessness due to hypoglycemia. ◉ Effects in Breastfed Infants A study of mothers taking beta-blockers during nursing found a numerically, but not statistically significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated. Of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. A prospective study of pregnant patients taking a beta-blocker asked mothers to complete a questionnaire about postpartum breastfeeding and any side effects in their breastfed infants. Two mothers reported taking metoprolol in unreported dosages while breastfeeding. Neither reported any adverse reactions in their breastfed infants. ◉ Effects on Lactation and Breastmilk Relevant published information on the effects of beta-blockade or metoprolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol. |
| 参考文献 | |
| 其他信息 |
Metoprolol succinate is an alcohol and a member of phenols.
Metoprolol Succinate is the succinate salt form of metoprolol, a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties and devoid of intrinsic sympathomimetic activity. Metoprolol succinate antagonizes beta 1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction, and consequently a diminished cardiac output. This agent may also reduce the secretion of renin with subsequent reduction in levels of angiotensin II thus decreasing sympathetic activation, including vasoconstriction, aldosterone secretion. A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS. See also: Metoprolol (has active moiety); Hydrochlorothiazide; metoprolol succinate (component of). |
| 分子式 |
C34H56N2O10
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|---|---|
| 分子量 |
652.8159
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| 精确质量 |
652.393
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| 元素分析 |
C, 62.55; H, 8.65; N, 4.29; O, 24.51
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| CAS号 |
98418-47-4
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| 相关CAS号 |
Metoprolol succinate;98418-47-4;Metoprolol-d7 hydrochloride;1219798-61-4;Metoprolol tartrate;56392-17-7;Metoprolol-d7;959787-96-3;(R)-Metoprolol-d7;1292907-84-6;(S)-Metoprolol-d7;1292906-91-2;Metoprolol-d5;959786-79-9; 51384-51-1; 56392-18-8 (HCl); 80274-67-5 (fumarate); 98418-47-4 (succinate)
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| PubChem CID |
62937
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| 外观&性状 |
White to off-white solid powder
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| 沸点 |
398.6ºC at 760 mmHg
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| 闪点 |
194.9ºC
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| LogP |
3.944
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| tPSA |
176.04
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| 氢键供体(HBD)数目 |
6
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| 氢键受体(HBA)数目 |
12
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| 可旋转键数目(RBC) |
21
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| 重原子数目 |
46
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| 分子复杂度/Complexity |
308
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| 定义原子立体中心数目 |
0
|
| SMILES |
O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C([H])(C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H].O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C([H])(C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H].O([H])C(C([H])([H])C([H])([H])C(=O)O[H])=O
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| InChi Key |
RGHAZVBIOOEVQX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/2C15H25NO3.C4H6O4/c2*1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3;5-3(6)1-2-4(7)8/h2*4-7,12,14,16-17H,8-11H2,1-3H3;1-2H2,(H,5,6)(H,7,8)
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| 化学名 |
butanedioic acid;1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
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| 别名 |
Metoprolol succinate; Dutoprol; Selozok; Toprol XL; Seloken-ZOK; H 93/26 succinate; Spesicor Dos; H 93/26 succinate; Toprol
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: 16.7~100 mg/mL (25.5~153.2 mM)
Water: ~100 mg/mL Ethanol: ~5 mg/mL |
|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 1.67 mg/mL (2.56 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。 配方 2 中的溶解度: ≥ 1.67 mg/mL (2.56 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。 View More
配方 3 中的溶解度: ≥ 1.67 mg/mL (2.56 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。 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 | 1.5318 mL | 7.6591 mL | 15.3182 mL | |
| 5 mM | 0.3064 mL | 1.5318 mL | 3.0636 mL | |
| 10 mM | 0.1532 mL | 0.7659 mL | 1.5318 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 |
| NCT02123056 | Active Recruiting |
Drug: Metoprolol Drug: Matching Placebo |
Vasovagal Syncope | University of Calgary | October 2014 | Phase 4 |
| NCT01608893 | Active Recruiting |
Drug: Carvedilol Drug: Metoprolol |
Atrial Fibrillation | University of Calgary | May 2012 | Not Applicable |
| NCT03278509 | Active Recruiting |
Drug: Metoprolol Succinate Drug: Bisoprolol |
Acute Myocardial InfarctionST Elevation Myocardial Infarction |
Karolinska Institutet | September 11, 2017 | Phase 4 |
| NCT03070184 | Active Recruiting |
Other: Exercise challenge Drug: Metoprolol Succinate ER |
Healthy Pre Hypertension |
University of Alabama at Birmingham |
April 30, 2017 | Phase 2 |
| NCT05741385 | Recruiting | Drug: Caffeine Drug: Warfarin sodium Drug: Omeprazole Drug: Metoprolol |
Liver Cirrhosis | Boehringer Ingelheim | April 25, 2023 | Not Applicable |
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