Angiotensin II receptor

依普罗沙坦 (SKF-108566J) 抑制 [125I]AII 与人肝膜（IC50 为 1.7 nM）和大鼠肠系膜动脉膜（IC50 为 1.5 nM）的结合。依普罗沙坦抑制兔主动脉平滑肌细胞中 AII 产生的细胞内 Ca2+ 水平的浓度依赖性增加[1]。

意识正常的血压大鼠静脉注射依普罗沙坦 (0.01-0.3 mg/kg) 引起 AII 升压剂量反应曲线的剂量依赖性平行变化。当意识正常、血压正常的大鼠十二指肠内或胃内给予依普罗沙坦（3-10 mg/kg）时，对 AII（250 ng/kg，静脉注射）的升压反应以剂量依赖性方式受到抑制。在 10 mg/kg，id 剂量下，可观察到对 AII 的升压反应的显着抑制持续三个小时[1]。

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Eprosartan（EPRO）是一种血管紧张素受体1型（AT-1）阻断剂，在大鼠局灶性脑缺血引起的缺血性卒中中表现出神经保护活性。本研究旨在阐明EPRO在大鼠中颈动脉闭塞（MCAO）诱导的缺血性卒中中的神经保护作用。56只雄性Wistar大鼠分为四组（每组14只）：假手术组、假接受EPRO（60mg/kg/天，po）组、缺血再灌注（IR）组和接受EPRO的IR（60mg/kg/d，po）小组。MCAO导致大鼠运动功能显著受损，同时刺激海马的炎症和凋亡途径。MCAO后，大脑中的AT1受体受到刺激，导致Janus激酶2/信号转导子和转录激活子3信号传导的激活，从而对海马体产生更多的神经炎症环境和破坏性作用。MCAO提高半胱氨酸天冬氨酸蛋白酶-3水平可增强神经元凋亡，与氧化应激生物标志物的神经退行性作用同步。EPRO预处理可对抗大鼠运动损伤，减少海马中的氧化和凋亡介质。EPRO的抗炎活性通过下调核因子κB和肿瘤坏死因子β水平以及（C-X-C基序）配体1信使RNA（mRNA）表达来揭示。此外，该研究证实了EPRO对缺氧诱导因子-1α及其后续炎症介质的独特途径的作用。此外，还观察到小窝蛋白-1 mRNA水平的上调，以及氧化应激标志物水平和脑水肿的降低。因此，EPRO通过减弱氧化、凋亡和炎症途径，在MCAO诱导的大鼠脑缺血中显示出神经保护作用[2]。

在大鼠和人类肾上腺皮质膜中，SK&F 108566分别以9.2和3.9 nM的IC50取代了特异性结合的[125I]AII。SK&F 108566还抑制了[125I]AII与人肝膜（IC50=1.7 nM）和大鼠肠系膜动脉膜（IC50=1.5 nM）的结合[1]。

在兔主动脉平滑肌细胞中，SK&F 108566引起AII诱导的细胞内钙水平升高的浓度依赖性抑制。在兔主动脉环中，SK&F 108566在AII浓度反应曲线中产生平行向右移动，而不影响最大收缩反应。数据的Schild分析得出KB值为0.26nM，斜率与1没有区别，表明竞争拮抗作用。SK&F 108566对兔主动脉对KCl、去甲肾上腺素或内皮素的收缩反应没有影响[1]。

In conscious normotensive rats, i.v. administration of SK&F 108566 (0.01-0.3 mg/kg) produced dose-dependent parallel shifts in the AII pressor dose-response curve. Administration of SK&F 108566 (3-10 mg/kg) intraduodenally or intragastrically to conscious normotensive rats resulted in a dose-dependent inhibition of the pressor response to AII (250 ng/kg, i.v.). At 10 mg/kg, i.d., significant inhibition of the pressor response to AII was observed for 3 hr. In this same rat model, SK&F 108566 had no effect on base-line pressure or on the pressor response to norepinephrine or vasopressin. The data demonstrate that SK&F 108566 is a potent, highly selective, competitive nonpeptide AII antagonist.

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3 mg/kg-10 mg/kg, administered by duodenal or gastric catheter

Rats

Absorption, Distribution and Excretion
Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.
Eprosartan is excreted in animal milk; it is not known whether eprosartan is excreted in human milk.
Plasma protein binding of eprosartan is high (approximately 98%) and constant over the concentration range achieved with therapeutic doses. The pooled population pharmacokinetic analysis from two Phase 3 trials of 299 men and 172 women with mild to moderate hypertension (aged 20 to 93 years) showed that eprosartan exhibited a population mean oral clearance (CL/F) for an average 60-year-old patient of 48.5 L/hr. The population mean steady-state volume of distribution (Vss/F) was 308 L. Eprosartan pharmacokinetics were not influenced by weight, race, gender or severity of hypertension at baseline. Oral clearance was shown to be a linear function of age with CL/F decreasing 0.62 L/hr for every year increase.
Eprosartan is eliminated by biliary and renal excretion, primarily as unchanged compound. Less than 2% of an oral dose is excreted in the urine as a glucuronide. There are no active metabolites following oral and intravenous dosing with (14)C eprosartan in human subjects. Eprosartan was the only drug-related compound found in the plasma and feces. Following intravenous (14)C eprosartan, about 61% of the material is recovered in the feces and about 37% in the urine. Following an oral dose of (14)C eprosartan, about 90% is recovered in the feces and about 7% in the urine.
Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Eprosartan plasma concentrations peak at 1 to 2 hours after an oral dose in the fasted state. Administering eprosartan with food delays absorption, and causes variable changes (<25%) in Cmax and AUC values which do not appear clinically important. Plasma concentrations of eprosartan increase in a slightly less than dose-proportional manner over the 100 mg to 800 mg dose range. The mean terminal elimination half-life of eprosartan following multiple oral doses of 600 mg was approximately 20 hours. Eprosartan does not significantly accumulate with chronic use.
For more Absorption, Distribution and Excretion (Complete) data for EPROSARTAN (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Eprosartan is not metabolized by the cytochrome P450 system. It is mainly eliminated as unchanged drug. Less than 2% of an oral dose is excreted in the urine as a glucuronide.
Following an oral dose of (14)C eprosartan, about 90% is recovered in the feces and about 7% in the urine. Approximately 20% of the radioactivity excreted in the urine was an acyl glucuronide of eprosartan with the remaining 80% being unchanged eprosartan.

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Biological Half-Life
The terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.
... The mean terminal elimination half-life of eprosartan following multiple oral doses of 600 mg was approximately 20 hours. ...
After oral administration of eprosartan to healthy volunteers ... the drug's terminal elimination half-life is typically 5-9 hours after oral administration. ...

Hepatotoxicity
Eprosartan has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: E* (Unproved but suspected rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of eprosartan during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ 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.

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Protein Binding
Plasma protein binding of eprosartan is high (approximately 98%) and constant over the concentration range achieved with therapeutic doses.

[1]. Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, SK&F 108566. J Pharmacol Exp Ther. 1992 Jan;260(1):175-81.

Eprosartan methanesulfonate is a methanesulfonate salt. It has a role as an antihypertensive agent. It contains an eprosartan.
Eprosartan Mesylate is the mesylate salt form of eprosartan, a non-biphenyl, non-tetrazole, nonpeptide angiotensin II antagonist with antihypertensive activity. Eprosartan mesylate antagonizes angiotensin II type I receptors in tissues such as vascular smooth muscle and the adrenal gland. This prevents angiotensin II-induced vasoconstriction and prevents angiotensin II-mediated stimulation of aldosterone secretion by the adrenal cortex, which decreases the excretion of sodium and water and increases the excretion of potassium.
See also: Eprosartan mesylate; hydrochlorothiazide (component of).

C23H24N2O4S.CH4O3S

520.62

520.133

C, 55.37; H, 5.42; N, 5.38; O, 21.51; S, 12.32

144143-96-4

Eprosartan;133040-01-4

5282474

White to off-white solid powder

1.26 g/cm3

660.6ºC

248 °C

353.3ºC

2.37E-18mmHg at 25°C

5.329

183.41

3

9

10

35

711

0

CCCCC1=NC=C(N1CC2=CC=C(C=C2)C(=O)O)/C=C(\CC3=CC=CS3)/C(=O)O.CS(=O)(=O)O

DJSLTDBPKHORNY-XMMWENQYSA-N

InChI=1S/C23H24N2O4S.CH4O3S/c1-2-3-6-21-24-14-19(12-18(23(28)29)13-20-5-4-11-30-20)25(21)15-16-7-9-17(10-8-16)22(26)27;1-5(2,3)4/h4-5,7-12,14H,2-3,6,13,15H2,1H3,(H,26,27)(H,28,29);1H3,(H,2,3,4)/b18-12+;

4-[[2-butyl-5-[(E)-2-carboxy-3-thiophen-2-ylprop-1-enyl]imidazol-1-yl]methyl]benzoic acid;methanesulfonic acid

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)

配方 1 中的溶解度: ≥ 2.08 mg/mL (4.00 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 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；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: ≥ 2.08 mg/mL (4.00 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 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，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: ≥ 2.08 mg/mL (4.00 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 20.8 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；
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