AT1/angiotensin II type 1 receptor (IC50 = 9.2 nM)

在完整的 RVSMC 细胞和膜制剂中，替米沙坦以浓度依赖性方式抑制 125I-AngII 与 AT1 受体的结合，IC50 为 9.2 ± 0.8 nM。在相同实验条件下，用血管紧张素II代替125I-AngII时，IC50值为2.9±0.5nM。未标记的替米沙坦和冷 AngII 的 IC50 值分别为 7.7 ± 1.8 nM 和 32.7 ± 5.7 nM，取代了 [3H]替米沙坦与 SMC 膜的特异性结合 [1]。替米沙坦 (100 μM) 处理可抑制三种 EAC 细胞系（OE19、OE33 和 SKGT-4）的生长，导致细胞周期停滞在 G0/G1 期，控制 EAC 细胞中与细胞周期相关的蛋白质，并激活 AMPK和细胞中的 mTOR 通路。 RTK、下游效应子和细胞周期相关蛋白均被替米沙坦抑制[5]。

在用替米沙坦（0.1、0.3 和 1 mg/kg）治疗的大鼠中，[3H]替米沙坦与活 RVSMC 表面的特异性结合已饱和，并在 1 小时内迅速增加至接近平衡。替米沙坦的解离半衰期 (t1/2) 为 75 分钟，与受体的解离非常缓慢，几乎比血管紧张素 II (AngII) 慢五倍，与坎地沙坦相当。替米沙坦以剂量依赖性方式降低体内对外源性 AngII 的血压反应 [1]。无论治疗是在动脉瘤形成之前还是之后开始，或者是持续短暂还是长期，替米沙坦（10 mg/kg/天）也能成功预防输注 PPE 后的动脉瘤发病机制。在动脉瘤主动脉中，替米沙坦治疗与 CCL5 和基质金属蛋白酶 2 和 9 的信使 RNA 水平降低有关，但对 PPARγ 控制的基因表达没有明显影响 [2]。在 5XFAD 动物中，替米沙坦（1 mg/kg/天）显着减少了神经元损失和空间获取障碍，尽管海马中的 NeuN 表达保持不变。当用替米沙坦（1 mg/kg/天）治疗时，5XFAD 小鼠的大脑中淀粉样蛋白和小胶质细胞的积累较少，这也会导致小胶质细胞极化为神经保护表型。然而，5XFAD 小鼠保持不变。 NEP 和 IDE 在特定大脑区域的表达水平 [3]。替米沙坦（0.05、0.1、1 mg/kg，口服）大大减少了大鼠的不动时间，除了显着降低大鼠的血液皮质醇、NO、IL-6 和 IL-1β 之外，还会对悲伤和焦虑产生不利影响。 4]。在携带 OE19 细胞异种移植物的小鼠中，替米沙坦（50 μg，腹腔注射）可将肿瘤生长降低 73.2%。此外，替米沙坦在体内显着改变了 miRNA 的表达[5]。

在本研究中，研究人员在体外研究了替米沙坦不可克服拮抗作用的分子基础，并将替米沙坦与厄贝沙坦和坎地沙坦的体内作用进行了比较。替米沙坦与AT1受体在体外表达AT1受体亚型的大鼠血管平滑肌细胞（RVSMC）上的结合和解离动力学被表征。在第二组实验中，将单次静脉注射剂量（0.1、0.3和1mg /kg）替米沙坦与厄贝沙坦（0.3、1.0、3.0和10.0 mg/kg）和坎地沙坦（0.3和1mg /kg）对清醒、血压正常的雄性Wistar大鼠的拮抗作用进行了比较。结果表明[(3)H]替米沙坦与活的RVSMC表面的特异性结合是饱和的，并在1 H内迅速增加达到平衡。替米沙坦与受体的解离非常缓慢，解离半衰期（t(1/2)）为75 min，与坎地沙坦相当，比血管紧张素II （AngII）慢近5倍。在体内，替米沙坦对外源性AngII剂量依赖性地减弱血压反应。当剂量>0.1 mg/kg时，阻断作用持续时间较长，在24小时内仍然显著。体外评估AT1受体阻断使用体外AngII受体结合试验显示类似的结果。当大鼠静脉给药时，替米沙坦的效力是厄贝沙坦的10倍，与坎地沙坦相当。综上所述，体外数据表明，替米沙坦的不可克服的拮抗作用至少部分是由于它与AT1受体的解离非常缓慢。

使用CCK-8细胞计数试剂盒，按照生产厂家说明书检测细胞增殖。简单地说，将5 × 103个细胞接种到96孔板的每孔中，并在100 μL添加10%胎牛血清的rpm -1640中培养。24 h后，每孔中加入arb（替米沙坦、伊贝沙坦、氯沙坦、缬沙坦粒径分别为0、1、10、100 μM）或载体，细胞再培养48 h。每孔中加入CCK-8试剂（10 μL）， 37℃孵育3 h，用酶标仪在450 nm处测定吸光度。[5]

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细胞周期与凋亡分析[5]
替米沙坦治疗后分析细胞周期谱以评估生长抑制作用。将OE19、OE33和SKGT-4细胞（1.0 × 106细胞，100mm直径培养皿）加100 μM替米沙坦或不加替米沙坦处理24-48 h。通过测定乙醇固定细胞中碘化丙啶（PI）标记的DNA的数量来分析细胞周期进程。将固定的细胞用PBS洗涤，然后在- 20°C下保存，用于流式细胞术分析。在分析当天，用冷PBS洗涤细胞，悬浮于100 μL含有10 μL RNase A （250 μg/mL）的PBS中，孵育30 min。每个悬浮液中加入110 μL PI (100 μg/mL)，在4℃下孵育至少30 min，然后进行分析。通过fitc偶联膜联蛋白V和PI的双染色分析凋亡和坏死细胞的死亡，这是基于暴露的磷脂酰丝氨酸将膜联蛋白V结合到凋亡细胞和PI标记晚期凋亡/坏死细胞的膜损伤。肿瘤细胞处理24和48小时，按照制造商的说明进行染色。流式细胞术采用Cytomics FC 500流式细胞仪。使用Kaluza软件测定细胞百分比。所有实验均为三次。

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替米沙坦部分激活过氧化物酶体增殖物激活受体γ (PPARγ)，有效降低血压，改善内皮功能和脂质代谢。局部血管中的肝细胞生长因子/间充质上皮转化因子（HGF/Met）系统在维持正常内皮功能中起关键作用。本研究旨在评估替米沙坦是否通过激活HGF/Met系统和/或PPARγ途径直接预防血管紧张素II （Ang II）诱导的内皮功能障碍（ED）。用Ang II （0.01-1 μM）、替米沙坦（0.1-10 μM）、SU11274 （5 μM）作为Met特异性抑制剂、GW9662 （10 μM）作为PPARγ拮抗剂单独或联合培养兔离体主动脉环6 h。Ang II明显抑制HGF、Met和PPARγ mRNA和蛋白的表达，并使主动脉环对乙酰胆碱的浓度累积松弛，其中1 μM Ang II的抑制作用最为显著。相反，替米沙坦显著增加HGF、Met和PPARγ的mRNA和蛋白表达，从而以剂量依赖性模式阻止Ang ii诱导的ED。而SU11274、GW9662或两者联合部分消除替米沙坦的保护作用，且SU11274的作用超过GW9662。上述结果表明，替米沙坦可通过选择性ppar γ调节途径抑制Ang ii诱导的体外兔主动脉环ED。此外，本研究首次表明，激活局部血管中的HGF/Met系统参与替米沙坦的保护机制。[2]

Male athymic mice (BALB/c-nu/nu; 6 weeks old; 20–25 g) were maintained under specific pathogen-free conditions using a laminar airflow rack. The mice had continuous free access to sterilized (γ-irradiated) food and autoclaved water. Each mouse was subcutaneously inoculated with OE19 cells (5 × 10~6 cells per animal) in the flank. One week later, the xenografts were identifiable as masses with a maximal diameter > 4 mm. The animals were randomly assigned to treatment with telmisartan (50 μg per day) or diluent only (control). The telmisartan group was intraperitoneally (i.p.) injected five times per week with 2 mg/kg telmisartan for four weeks; the control group was administered 5% DMSO alone for four weeks. Tumor growth was monitored daily by the same investigators (S. Fujihara and A. Morishita), and tumor size was measured weekly. The tumor volume (mm3) was calculated as the tumor length (mm) × tumor width (mm)2/2. All animals were sacrificed on day 22 after treatment, and all animals survived during this period. Between-group differences in tumor growth were analyzed by two-way ANOVA.[5]

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The renin-angiotensin system (RAS) is a major circulative system engaged in homeostasis modulation. Angiotensin II (Ang II) serves as its main effector hormone upon binding to its primary receptor, Ang II receptor type 1 (AT1R). It is well established that an intrinsic independent brain RAS exists. Abnormal AT1R activation both in the periphery and in the brain probably contributes to the development of Alzheimer's disease (AD) pathology that is characterized, among others, by brain inflammation. Moreover, treatment with drugs that block AT1R (AT1R blockers, ARBs) ameliorates most of the clinical risk factors leading to AD. Previously we showed that short period of intranasal treatment with telmisartan (a brain penetrating ARB) reduced brain inflammation and ameliorated amyloid burden (a component of Alzheimer's plaques) in AD transgenic mouse model. In the present study, we aimed to examine the long-term effect of intranasally administrated telmisartan on brain inflammation features including microglial activation, astrogliosis, neuronal loss and hippocampus-dependent cognition in five-familial AD mouse model (5XFAD). Five month of intranasal treatment with telmisartan significantly reduced amyloid burden in the cortex and hippocampus of 5XFAD mice as compared with the vehicle-treated 5XFAD group. Similar effects were also observed for CD11b staining, which is a marker for microglial accumulation. Telmisartan also significantly reduced astrogliosis and neuronal loss in the cortex of 5XFAD mice compared with the vehicle-treated group. Improved spatial acquisition of the 5XFAD mice following long-term intranasal administration of telmisartan was also observed. Taken together, our data suggest a significant role for AT1R blockage in mediating neuronal loss and cognitive behavior, possibly through regulation of amyloid burden and glial inflammation.[3]

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Background: Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats.[4]
Methods: Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-1β).[4]
Results: Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1β (p<0.001). TMS antagonized depression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1β (p<0.001).[4]
Conclusions: Low dose TMS and its combination with metformin normalizes depressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID.

Absorption, Distribution and Excretion
Oral telmisartan follows nonlinear pharmacokinetics over the dose range of 20 mg to 160 mg. Both Cmax and AUC present greater than proportional increases at higher doses. With once-daily dosing, telmisartan has trough plasma concentrations of about 10% to 25% of peak plasma concentrations. The absolute bioavailability of telmisartan depends on the dosage. At 40 mg and 160 mg, the bioavailability was 42% and 58%, respectively. Food slightly decreases bioavailability. For instance, when the 40 mg dose is administered with food, a decrease of about 6% is seen, and with the 160 mg dose, there is a decrease of about 20%.
Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Telmisartan has a volume of distribution of approximately 500 liters.
Telmisartan has a total plasma clearance of >800 mL/min.
Following either intravenous or oral administration of (14)C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and a1 - acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.
It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats.
To study the pharmacolkinetics of telmisartan in healthy Chinese male subjects after oral administration of two dosage levels, 36 healthy subjects were divided into two groups and given a single oral dose of 40 or 80 mg telmisartan (CAS 144701-48-4, MicardisPlus). A sensitive liquid chromatography-tandem mass spectrometry method (LC-MS-MS) was used for the determination of telmisartan in plasma. Both, a non-compartmental and compartmental method were used for analysis of parameters of kinetics. The main pharmacokinetic parameters of the 40 mg and 80 mg regimen group were as follows: t(max) (1.76 +/- 1.75) h, (1.56 +/- 1.09) h, C(max) (163.2 +/- 128.4) ng/mL, (905.7 +/- 583.4) ng/mL, t1/2 (23.6 +/- 10.8) h, (23.0 +/- 6.4) h, AUC(o-t) (1456 +/- 1072) ng x h/mL, (6759 +/- 3754) ng x h/mL, AUC(o-infinity (1611 +/- 1180) ng x h/mL, (7588 +/- 4661) ng x h/mL, respectively. After dose normalization, there was significant difference for main pharmacokinetic parameters C(max) AUC(o-t) and AUC(o-infinity) between two dosage level groups. The plasma concentration-time profile of telmisartan was characterized by a high degree of inter-individual variability and the disposition of telmisartan in healthy Chinese subjects was dose-dependent. The pharmacokinetic parameters C(max) and AUC(o-inifinity) of the 80 mg regimen group increased to about 5-fold compared to that of the 40 mg regimen group, but there was no significant difference for t(max) and t1/2 between the two dose groups.

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Metabolism / Metabolites
Minimally metabolized by conjugation to form a pharmacologically inactive acyl-glucuronide, the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.

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Biological Half-Life
Telmisartan displays bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.
Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours.

Toxicity Summary
IDENTIFICATION AND USE: Telmisartan is a white to slightly yellowish solid that is formulated into oral tablets. Telmisartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used alone or in combination with other classes of antihypertensive in the management of hypertension. It is also indicated for reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors. HUMAN EXPOSURE AND TOXICITY: The most likely manifestations of telmisartan overdose include hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. The use of telmisartan during pregnancy is contraindicated. While use during the first trimester does not suggest a risk of major anomalies, use during the second and third trimester may cause teratogenicity and severe fetal and neonatal toxicity. Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, premature birth, and patent ductus arteriosus. Anuria-associated oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension that are resistant to both pressor agents and volume expansion may occur in the newborn following in utero exposure to telmisartan. ANIMAL STUDIES: Telmisartan was not carcinogenic when administered by dietary administration to mice and rats for up to 2 years. Also, the fertility of male and female rats was unaffected by administration of the drug. No teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses as high as 50 mg/kg/day or pregnant rabbits at oral doses as high as 45 mg/kg/day. However, in rabbits, embryolethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed. In rats, the maternally toxic dose was 15 mg/kg/day. When this dose was administered during late gestation and lactation it produced adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. Genotoxicity assays did not reveal any drug-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella and E. coli (Ames test), a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse micronucleus test.

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Hepatotoxicity
Telmisartan 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
No information is available on the use of telmisartan during breastfeeding and the manufacturer advises avoidance of breastfeeding during telmisartan therapy. 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
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and alpha 1-acid glycoprotein. Binding is not dose-dependent.

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Interactions
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of non-steroidal anti-inflammatory agents (NSAIDs), including selective selective cyclooxygenase-2 (COX-2) inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.
Do not co-administer aliskiren with Micardis in patients with diabetes. Avoid use of aliskiren with Micardis in patients with renal impairment (GFR <60 mL/min).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including Micardis. Therefore, monitor serum lithium levels during concomitant use.
Co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of ramipril 2.3- and 2.1-fold, respectively, and Cmax and AUC of ramiprilat 2.4- and 1.5-fold, respectively. In contrast, Cmax and AUC of telmisartan decrease by 31% and 16%, respectively. When co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. Concomitant use of Micardis and ramipril is not recommended.
For more Interactions (Complete) data for TELMISARTAN (6 total), please visit the HSDB record page.

[1]. In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1089-95.

[2]. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. J Vasc Surg. 2017 Apr 20. pii: S0741-5214(17)30100-3.

[3]. Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice. Brain Behav Immun. 2017 Apr 3.

[4]. Telmisartan attenuates diabetes induced depression in rats. Pharmacol Rep. 2017 Apr;69(2):358-364.

[5]. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathway in vitro and in vivo. Oncotarget. 2017 Jan 31;8(5):8536-8549.

Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents
Micardis is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. ... Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. /Micardis/ may be used alone or in combination with other antihypertensive agents /Included in US product labeling/
Micardis is indicated for reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors. High risk for cardiovascular events can be evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin dependent) with evidence of end-organ damage. Micardis can be used in addition to other needed treatment (such as antihypertensive, antiplatelet or lipid-lowering therapy). Studies of telmisartan in this setting do not exclude the possibility that telmisartan may not preserve a meaningful fraction of the effect of the ACE inhibitor to which it was compared. Consider using the ACE inhibitor first, and, if it is stopped for cough only, consider re-trying the ACE inhibitor after the cough resolves. /Included in US product label/
Both angiotensin II receptor antagonists /including telmisartan/ and ACE inhibitors have been shown to slow the rate of progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy, and use of a drug from either class is recommended in such patients. /NOT included in US product label/
For more Therapeutic Uses (Complete) data for TELMISARTAN (8 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue Micardis as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Micardis as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Micardis, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Neonates with a history of in utero exposure to Micardis: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./
For more Drug Warnings (Complete) data for TELMISARTAN (17 total), please visit the HSDB record page.

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Pharmacodynamics
Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT₁ receptor subtype. It has the highest affinity for the AT₁ receptor among commercially available ARBs and has minimal affinity for the AT₂ receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.

C33H30N4O2

514.62

514.236

C, 77.02; H, 5.88; N, 10.89; O, 6.22

144701-48-4

Telmisartan-d3;1189889-44-8;Telmisartan-d7;1794754-60-1;Telmisartan-d4;Telmisartan-13C,d3;1261396-33-1; 144701-48-4; 528560-93-2 (methyl ester)

65999

White to off-white solid powder

1.2±0.1 g/cm3

771.9±70.0 °C at 760 mmHg

261-263°C

420.6±35.7 °C

0.0±2.8 mmHg at 25°C

1.667

7.73

72.94

1

4

7

39

831

0

O=C(C1=CC=CC=C1C2=CC=C(CN3C4=CC(C5=NC6=CC=CC=C6N5C)=CC(C)=C4N=C3CCC)C=C2)OC

RMMXLENWKUUMAY-UHFFFAOYSA-N

InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39)

4-((1,7-dimethyl-2-propyl-1H,3H-[2,5-bibenzo[d]imidazol]-3-yl)methyl)-[1,1-biphenyl]-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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: ≥ 0.67 mg/mL (1.30 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 6.7 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: ≥ 0.67 mg/mL (1.30 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 6.7 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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配方 3 中的溶解度: 3 mg/mL (5.83 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*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 4 中的溶解度: 3.33 mg/mL (6.47 mM) in 17% Polyethylene glycol 12-hydroxystearate in Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声和加热处理
*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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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。