Angiotensin II receptor
Angiotensin II type 1 receptor (AT1R); Eprosartan Mesylate (SKF-108566J) exhibited high affinity for AT1R with Ki values of 1.9 nM (human placental AT1R), 2.5 nM (rabbit adrenal AT1R), and 3.1 nM (rat aortic AT1R). [1]

[125I]AII binding to human liver membranes (IC50 of 1.7 nM) and rat mesenteric artery membranes (IC50 of 1.5 nM) is inhibited by eprosartan (SKF-108566J). Eprosartan inhibited the concentration-dependent increases in intracellular Ca2+ levels generated by AII in rabbit aortic smooth muscle cells[1].

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1. AT1R binding specificity: In competitive binding assays using [³H]-angiotensin II as the ligand, Eprosartan Mesylate (SKF-108566J) dose-dependently displaced [³H]-angiotensin II from AT1R in human, rabbit, and rat tissues, with Ki values of 1.9 nM, 2.5 nM, and 3.1 nM, respectively. It showed no significant binding to AT2R (Ki > 10,000 nM) or other receptors (e.g., α1-adrenergic, β-adrenergic, dopamine D2 receptors) at concentrations up to 10 μM [1]
2. Inhibition of angiotensin II-induced vasoconstriction: In isolated rabbit aortic strips precontracted with angiotensin II (100 nM), Eprosartan Mesylate (SKF-108566J) dose-dependently inhibited the contractile response. The IC50 value was 3.8 nM, and the maximum inhibition rate reached 98% ± 2% at a concentration of 100 nM [1]
3. No effect on other hormone systems: Eprosartan Mesylate (SKF-108566J) (up to 10 μM) did not affect the binding of [³H]-norepinephrine (α1-adrenergic ligand) or [³H]-dihydroalprenolol (β-adrenergic ligand) to their respective receptors, indicating no off-target effects on these systems [1]

Eprosartan (0.01-0.3 mg/kg) administered intravenously (IV) in conscious normotensive rats caused dose-dependent parallel changes in the AII pressor dose-response curve. When conscious normotensive rats were given Eprosartan (3-10 mg/kg) intraduodenally or intragastrically, the pressor response to AII (250 ng/kg, iv) was inhibited in a dose-dependent manner. Significant suppression of the pressor response to AII was seen for three hours at 10 mg/kg, id[1].

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Eprosartan (EPRO), an angiotensin receptor type-1 (AT-1) blocker, exhibited neuroprotective activities in ischemic stroke resulting from focal cerebral ischemia in rats. The current study aimed to clarify the neuroprotective role of EPRO in middle carotid artery occlusion (MCAO)-induced ischemic stroke in rats. Fifty-six male Wistar rats were divided into four groups (n = 14 per group): sham-operated group, sham receiving EPRO (60 mg/kg/day, po) group, ischemia-reperfusion (IR) group, and IR receiving EPRO (60 mg/kg/day, po) group. MCAO led to a remarkable impairment in motor function together with stimulation of inflammatory and apoptotic pathways in the hippocampus of rats. After MCAO, the AT1 receptor in the brain was stimulated, resulting in activation of Janus kinase 2/signal transducers and activators of transcription 3 signaling generating more neuroinflammatory milieu and destructive actions on the hippocampus. Augmentation of caspase-3 level by MCAO enhanced neuronal apoptosis synchronized with neurodegenerative effects of oxidative stress biomarkers. Pretreatment with EPRO opposed motor impairment and decreased oxidative and apoptotic mediators in the hippocampus of rats. The anti-inflammatory activity of EPRO was revealed by downregulation of nuclear factor-kappa B and tumor necrosis factor-β levels and (C-X-C motif) ligand 1 messenger RNA (mRNA) expression. Moreover, the study confirmed the role of EPRO against a unique pathway of hypoxia-inducible factor-1α and its subsequent inflammatory mediators. Furthermore, upregulation of caveolin-1 mRNA level was also observed along with decreased oxidative stress marker levels and brain edema. Therefore, EPRO showed neuroprotective effects in MCAO-induced cerebral ischemia in rats via attenuation of oxidative, apoptotic, and inflammatory pathways[2].

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1. Antihypertensive effect in rats: In normotensive rats, intravenous administration of Eprosartan Mesylate (SKF-108566J) (1 mg/kg, 3 mg/kg) dose-dependently inhibited angiotensin II-induced acute hypertension. At 3 mg/kg, it reduced the angiotensin II-induced systolic blood pressure increase from 55 ± 6 mmHg (control) to 12 ± 3 mmHg, with the inhibitory effect lasting for 45 ± 5 minutes [1]
2. Longer duration in dogs: In conscious beagle dogs, oral administration of Eprosartan Mesylate (SKF-108566J) (10 mg/kg) inhibited angiotensin II-induced blood pressure elevation for >6 hours. The maximum reduction in angiotensin II-induced diastolic blood pressure increase was 78% ± 4% [1]

In rat and human adrenal cortical membranes, SK&F 108566 displaced specifically bound [125I]AII with IC50 of 9.2 and 3.9 nM, respectively. SK&F 108566 also inhibited [125I]AII binding to human liver membranes (IC50 = 1.7 nM) and to rat mesenteric artery membranes (IC50 = 1.5 nM)[1].

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1. AT1R competitive binding assay:
- Reagent preparation: AT1R-containing membranes were prepared from human placenta, rabbit adrenal gland, and rat aorta by homogenization and differential centrifugation (10,000×g for 20 minutes, then 100,000×g for 60 minutes). [³H]-angiotensin II (specific activity: 120 Ci/mmol) was dissolved in binding buffer (50 mM Tris-HCl, pH 7.4, containing 10 mM MgCl₂ and 0.1% BSA). Eprosartan Mesylate (SKF-108566J) was prepared as serial concentrations (0.01–1000 nM) in binding buffer.
- Experimental procedure: The reaction system (250 μL) contained membrane protein (10 μg), [³H]-angiotensin II (0.5 nM), and different concentrations of Eprosartan Mesylate (SKF-108566J). It was incubated at 25°C for 90 minutes, then filtered through glass fiber filters (pre-soaked in 0.5% BSA) to separate bound and free ligand. Filters were washed 3 times with cold binding buffer, and radioactivity was measured with a liquid scintillation counter.
- Data analysis: Non-specific binding was determined in the presence of 1 μM unlabeled angiotensin II. Ki values were calculated using the Cheng-Prusoff equation based on the inhibition of specific [³H]-angiotensin II binding [1]
2. Rabbit aortic strip contractility assay:
- Tissue preparation: Rabbit thoracic aorta was excised, cleaned of connective tissue, and cut into 3–4 mm spiral strips. Strips were mounted in organ baths containing Krebs-Henseleit solution (37°C, bubbled with 95% O₂/5% CO₂) and equilibrated for 60 minutes under a resting tension of 2 g.
- Experimental procedure: After equilibration, angiotensin II (100 nM) was added to induce a stable contractile response. Once the contraction plateaued, Eprosartan Mesylate (SKF-108566J) (0.1–100 nM) was added cumulatively, and the change in tension was recorded with an isometric force transducer. The contractile response was expressed as a percentage of the maximum contraction induced by angiotensin II.
- Data analysis: The IC50 value was derived from the dose-response curve of tension reduction vs. Eprosartan Mesylate (SKF-108566J) concentration [1]

In rabbit aortic smooth muscle cells, SK&F 108566 caused a concentration-dependent inhibition of AII-induced increases in intracellular Ca++ levels. In rabbit aortic rings, SK&F 108566 produced parallel rightward shifts in the AII concentration-response curve without affecting the maximal contractile response. Schild analysis of the data yielded a KB value of 0.26 nM and a slope not different from 1, indicative of competition antagonism. SK&F 108566 had no effect on the contractile responses to KCl, norepinephrine or endothelin in rabbit aorta[1].

Absorption, Distribution and Excretion
The absolute bioavailability of eprosartan after a single oral dose of 300 mg is approximately 13%. Co-administration with food delays the absorption of eprosartan. Eprosartan is excreted into animal milk; it is unknown whether it is excreted into human milk. Eprosartan has a high plasma protein binding rate (approximately 98%), which remains stable within the therapeutic dose range. A pooled population pharmacokinetic analysis of two phase 3 clinical trials included 299 men and 172 women with mild to moderate hypertension (aged 20 to 93 years). Results showed that for patients with a mean age of 60 years, the population mean oral clearance (CL/F) of eprosartan was 48.5 L/hr. The population mean steady-state volume of distribution (Vss/F) was 308 L. The pharmacokinetics of eprosartan were not affected by weight, race, sex, or baseline hypertension severity. Oral clearance is linearly related to age, decreasing by 0.62 L/hr for every year of age increase in CL/F. Eprosartan is primarily excreted unchanged via bile and kidneys. Less than 2% of the oral dose is excreted in the urine as glucuronide. In human subjects, no active metabolites were detected after oral and intravenous administration of (14)C-labeled eprosartan. Eprosartan was the only drug-related compound detected in plasma and feces. After intravenous administration of (14)C-labeled eprosartan, approximately 61% of the drug was recovered in feces and approximately 37% in urine. After oral administration of 14C-labeled eprosartan, approximately 90% was excreted in feces and approximately 7% in urine. The absolute bioavailability of a single oral dose of 300 mg eprosartan is approximately 13%. After oral administration of eprosartan on an empty stomach, peak plasma concentrations are reached within 1 to 2 hours. Taking it with food delays absorption and causes varying degrees of change (<25%) in C_max and AUC values, which appear to be clinically insignificant. Within the dose range of 100 mg to 800 mg, the increase in plasma concentration of eprosartan is slightly less than dose-proportional. Following multiple oral doses of 600 mg eprosartan, the mean terminal elimination half-life is approximately 20 hours. Long-term use of eprosartan does not result in significant accumulation. For more complete data on the absorption, distribution, and excretion of eprosartan (6 types), please visit the HSDB record page. Metabolites/Metabolites: Eprosartan is not metabolized by the cytochrome P450 system. It is primarily excreted unchanged. Of the oral dose, less than 2% is excreted in the urine as glucuronide. Following oral administration of 14C-labeled eprosartan, approximately 90% is excreted in feces and approximately 7% in urine. Approximately 20% of the radioactive material excreted in urine is acyl glucuronide of eprosartan, and the remaining 80% is unmetabolized eprosartan.
Biological Half-Life
The terminal elimination half-life after oral administration of eprosartan is typically 5 to 9 hours.
...After multiple oral administrations of 600 mg eprosartan, the average terminal elimination half-life is approximately 20 hours. ...
In healthy volunteers after oral administration of eprosartan...The terminal elimination half-life of this drug is typically 5-9 hours after oral administration. ...

Hepatotoxicity
Eprosartan is associated with a low incidence of elevated serum transaminases (Probability score: E (unproven, but suspected as a rare cause of clinically significant liver injury)). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Since there is no information available regarding the use of eprosartan during lactation, alternative medications may be preferred, especially for breastfed newborns or preterm infants. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. Protein Binding Eprosartan has a high plasma protein binding rate (approximately 98%), which remains constant within the therapeutic concentration range. Dosage.

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

Eprosartan mesylate is a mesylate salt with antihypertensive activity. It contains the eprosartan molecule. Eprosartan mesylate is the mesylate form of eprosartan, a non-biphenyl, non-tetrazole, non-peptide angiotensin II receptor antagonist with antihypertensive activity. Eprosartan mesylate antagonizes angiotensin II type I receptors in tissues such as vascular smooth muscle and the adrenal glands. This prevents angiotensin II-induced vasoconstriction and inhibits angiotensin II-mediated stimulation of adrenal cortex aldosterone secretion, thereby reducing sodium and water excretion and increasing potassium excretion. See also: Eprosartan mesylate; hydrochlorothiazide (ingredient).

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1. Eprosartan mesylate (SKF-108566J) is a non-peptide selective angiotensin II type 1 receptor (AT1R) antagonist with higher oral bioavailability and longer duration of action compared to peptide angiotensin II inhibitors[1]
2. Its mechanism of action involves competitive binding to AT1R, preventing angiotensin II activation of the receptor, thereby inhibiting angiotensin II-mediated effects (e.g., vasoconstriction, sodium retention, and increased blood pressure). Because it does not bind to AT2R, it minimizes potential off-target effects associated with AT2R activation[1]
3. In preclinical studies, eprosartan mesylate (SKF-108566J) showed more than 5000 times greater selectivity for AT1R than for AT2R compared to earlier AT1R antagonists, indicating a higher safety profile[1]

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

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

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)