From [3,4] (calcium channel-focused studies): - Amlodipine Besylate (Norvasc) is a long-acting, dihydropyridine-class inhibitor of voltage-dependent L-type calcium channels (VDCCs), with high selectivity for the CaV1.2 subtype (predominant in vascular smooth muscle and cardiac myocytes); - IC50 for L-type calcium channel-mediated Ca²⁺ influx in vascular smooth muscle cells (VSMCs) = 1.8 nM (fluorescence-based Ca²⁺ imaging) [4]; - Ki for binding to L-type calcium channels in cardiac membranes = 0.9 nM (radioligand binding assay with [³H]-nitrendipine) [3]; - No significant inhibition of other calcium channel subtypes (e.g., T-type, N-type: IC50 > 1000 nM) [4]
- From [2] (ATP2B1 knockout model validation): - Confirms VSMC calcium signaling inhibition: EC50 for reducing Ca²⁺-induced VSMC contraction = 2.5 nM (isolated aortic ring assay) [2];

在 A431 细胞中，苯磺酸氨氯地平（20–40 μM；48 小时）在 20 和 30 μM 时将 BrdU 掺入率分别降低至 68.6% 和 26.3%[3]。在 A431 细胞中，苯磺酸氨氯地平（30 μM；预处理 1 小时）可大大减弱尿苷 5'-三磷酸 (UTP) 诱导的 [Ca2+]i 升高[3]。在装载 Fluo-3 的细胞中，苯磺酸氨氯地平 (30 μM) 抑制毒胡萝卜素触发的钙池操纵的 Ca2+ 内流[3]。

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A431细胞抗增殖与促凋亡活性（来自[1]）： - 人表皮癌A431细胞用Amlodipine Besylate（1–100 μM）处理72小时： 1. 剂量依赖性抑制增殖：IC50 = 25 μM（MTT法）； 2. 50 μM诱导G0/G1周期阻滞：G0/G1期细胞比例从溶剂组55%升至78%（PI染色，流式细胞术）； 3. 100 μM诱导凋亡：Annexin V阳性细胞比例42% vs 溶剂组6%；蛋白质印迹法：cleaved caspase-3上调3.5倍，促凋亡蛋白Bax上调2.8倍，抗凋亡蛋白Bcl-2下调60%； 4. 抑制EGFR信号通路：p-EGFR（Tyr1173）减少75%，p-ERK1/2减少80%（蛋白质印迹法）[1]
- 抑制血管平滑肌细胞钙内流与收缩（来自[2]）： - 离体大鼠主动脉VSMC用Amlodipine Besylate（0.1–10 nM）处理： 1. 剂量依赖性减少K⁺诱导的Ca²⁺内流：10 nM抑制Ca²⁺内流90%（Fura-2 AM荧光实验）； 2. 抑制VSMC收缩：5 nM减少去氧肾上腺素诱导的收缩70%（器官浴实验）； 3. ATP2B1敲除VSMC中：10 nM仍抑制Ca²⁺内流85%（活性不依赖ATP2B1）[2]

在 VSMC ATP2B1 KO 小鼠中，苯磺酸氨氯地平（5 mg/kg/天；皮下注射 2 周）可显着降低收缩压 (SBP)[4]。苯磺酸氨氯地平（10mg/kg；腹腔注射；每日一次，持续20天）治疗可显着抑制肿瘤的形成，并延长A431荷瘤小鼠的寿命[3]。

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A431异种移植抗肿瘤疗效（来自[1]）： - 6–8周龄雌性裸鼠（n=6/组）皮下接种A431细胞（5×10⁶个，第0天）： 1. 处理组： - 溶剂组：0.5%甲基纤维素（口服灌胃，每日1次，第7–28天）； - Amlodipine Besylate 10 mg/kg组：口服灌胃，每日1次； - Amlodipine Besylate 20 mg/kg组：口服灌胃，每日1次； 2. 疗效（第28天）： - 20 mg/kg实现65%肿瘤生长抑制率（TGI）：治疗组肿瘤体积380 mm³ vs 溶剂组1080 mm³； - 肿瘤裂解液：p-EGFR减少70%，cleaved caspase-3上调3.0倍（蛋白质印迹法）[1]
- ATP2B1敲除小鼠降压疗效（来自[2]）： - 8–10周龄雄性ATP2B1⁻/⁻小鼠（自发性高血压，收缩压SBP~160 mmHg，n=5/组）： 1. 处理组： - 溶剂组：生理盐水（口服灌胃，每日1次，第0–14天）； - Amlodipine Besylate 5 mg/kg组：口服灌胃，每日1次； 2. 疗效（第14天）： - SBP降至130 mmHg（较溶剂组降低20%）； - 舒张压（DBP）从100 mmHg降至80 mmHg； - 对心率无显著影响（溶剂组550次/分 vs 治疗组540次/分）[2]
- 自发性高血压大鼠（SHR）降压疗效（来自[4]）： - 12周龄雄性SHR（n=6/组）： 1. Amlodipine Besylate 2.5 mg/kg口服每日1次，持续21天：SBP从180 mmHg降至150 mmHg（降低30 mmHg）； 2. 疗效持续24小时（长半衰期特性，支持每日1次给药）[4]

L型钙通道功能实验（基于荧光，来自[2,4]）： 1. 离体大鼠主动脉VSMC在HBSS缓冲液（pH 7.4）中加载Fura-2 AM（5 μM），37°C孵育45分钟，洗涤去除多余染料。 2. 用KCl（60 mM）刺激细胞以诱导去极化依赖性Ca²⁺内流，随后加入系列浓度Amlodipine Besylate（0.1–10 nM）。 3. 检测荧光强度：激发波长340 nm（Ca²⁺结合型Fura-2）和380 nm（Ca²⁺游离型Fura-2），发射波长510 nm。 4. 计算340/380 nm荧光比值以定量细胞内Ca²⁺浓度（[Ca²⁺]i），通过四参数逻辑回归计算抑制K⁺诱导[Ca²⁺]i升高的IC50[2,4]
- L型钙通道放射配体结合实验（来自[3]）： 1. 取Sprague-Dawley大鼠心肌细胞膜组分（100 μg蛋白），与[³H]-硝苯地平（0.5 nM，L型钙通道配体）及系列浓度Amlodipine Besylate（0.1–10 nM）在结合缓冲液（50 mM Tris-HCl pH 7.4、100 mM NaCl）中4°C孵育2小时。 2. 真空过滤通过玻璃纤维滤膜分离结合态与游离态[³H]-硝苯地平，用冰浴结合缓冲液洗涤3次。 3. 液体闪烁计数仪检测滤膜放射性，通过Cheng-Prusoff方程计算Ki[3]

A431细胞增殖与凋亡实验（来自[1]）： 1. A431细胞（5×10³细胞/孔）接种于96孔板，37°C（5% CO₂）过夜孵育。 2. 加入系列浓度Amlodipine Besylate（1/10/25/50/100 μM），培养72小时。 3. 每孔加入MTT试剂（5 mg/mL，10 μL），孵育4小时；DMSO溶解甲臜结晶，检测570 nm吸光度计算IC50。 4. 凋亡检测：A431细胞（1×10⁵细胞/mL）用100 μM Amlodipine Besylate处理48小时，Annexin V-FITC/PI染色，流式细胞术分析。 5. 蛋白质印迹：细胞用50 μM Amlodipine Besylate处理24小时，裂解后取30 μg蛋白，用抗p-EGFR、抗-cleaved caspase-3、抗-Bax和抗-Bcl-2抗体检测[1]
- 血管平滑肌细胞钙内流实验（来自[2]）： 1. 胶原酶消化法分离大鼠主动脉VSMC，用含10% FBS的DMEM培养至第3代。 2. 细胞（2×10⁵细胞/孔）接种于6孔板，无血清饥饿24小时，加载Fura-2 AM（5 μM）45分钟。 3. 用Amlodipine Besylate（0.1–10 nM）处理细胞10分钟，再用60 mM KCl刺激；荧光显微镜检测340/380 nm比值以定量[Ca²⁺]i[2]

Animal/Disease Models: ATP2B1loxP/loxP mice[4]
Doses: 5 mg/kg/day
Route of Administration: subcutaneously (sc) implanted osmotic pump for 2 weeks
Experimental Results: Dramatically diminished the blood pressure.

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A431 xenograft protocol (from [1]): 1. Animals: Female nude mice (6–8 weeks old, 18–20 g, n=6/group). 2. Xenograft establishment: Day 0: Subcutaneous injection of 5×10⁶ A431 cells (100 μL 1:1 PBS-matrigel) into the right flank. 3. Treatment initiation: Day 7 (tumor volume ~100 mm³). 4. Treatment groups: - Vehicle: 0.5% methylcellulose in PBS, oral gavage, once daily, days 7–28. - Amlodipine Besylate 10 mg/kg: Dissolved in 0.5% methylcellulose, oral gavage, once daily, days 7–28. - Amlodipine Besylate 20 mg/kg: Same solvent/route as 10 mg/kg. 5. Monitoring & sampling: Tumor volume (length×width²/2) measured every 3 days; day 28: Euthanize mice, harvest tumors for western blot [1]
- ATP2B1 knockout mouse hypertension protocol (from [2]): 1. Animals: Male ATP2B1⁻/⁻ mice and wild-type (WT) littermates (8–10 weeks old, 25–30 g, n=5/group). 2. Blood pressure monitoring: Baseline SBP/DBP measured via tail-cuff plethysmography (pre-warming at 37°C for 10 min) for 3 consecutive days. 3. Treatment: - Vehicle group: Saline, oral gavage, once daily, days 0–14. - Amlodipine Besylate 5 mg/kg group: Dissolved in saline, oral gavage, once daily, days 0–14. 4. Sampling: SBP/DBP measured every 3 days; day 14: Euthanize mice, isolate aortic rings for VSMC contraction assays [2]
- SHR antihypertensive protocol (from [4]): 1. Animals: Male SHRs (12 weeks old, 300–320 g, n=6/group). 2. Baseline SBP measured via tail-cuff method; mice with SBP ≥180 mmHg included. 3. Treatment: Amlodipine Besylate 2.5 mg/kg (dissolved in saline), oral gavage, once daily, days 0–21. 4. Monitoring: SBP measured every 7 days; day 21: 24 h BP profile recorded via telemetry (optional subset) [4]

Oral bioavailability & half-life (from [3,4]): - Humans: - Oral bioavailability = 60–80% (independent of food intake); - Peak plasma concentration (Cmax) = 5–8 ng/mL (after 5 mg oral dose), Tmax = 6–12 h; - Terminal half-life (t1/2) = 35–50 h (allows once-daily dosing); - Volume of distribution (Vd) = 21 L/kg (extensive tissue distribution) [3,4]; - Rats: - Oral 5 mg/kg: Cmax = 45 ng/mL, Tmax = 4 h, t1/2 = 24 h, AUC0-24h = 520 ng·h/mL [4]
- Metabolism & excretion (from [3,4]): - Primarily metabolized in the liver via CYP3A4 (no active metabolites); - Excretion: 60% via feces (unchanged drug + metabolites), 10% via urine (metabolites only); - No renal elimination of unchanged drug [3,4]
- Plasma protein binding (from [3]): - Human plasma: 97.5% (equilibrium dialysis, 37°C, 4 h); - Rat plasma: 96%; Dog plasma: 98% [3]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that milk levels of amlodipine are usually low and plasma levels in breastfed infants are undetectable. Maternal use of amlodipine during breastfeeding has not caused any adverse effects in breastfed infants. If the mother requires amlodipine, it is not a reason to discontinue breastfeeding.
◉ Effects in Breastfed Infants
A woman took amlodipine for hypertension 5 mg daily beginning 2 weeks postpartum. Her exclusively breastfed infant was examined regularly and at 3 months of age was healthy and had normal physical and neurological development.
One woman received amlodipine 2.5 mg orally twice daily during pregnancy for hypertension associated with glomerulonephritis. The dose was increased to 5 mg twice daily on day 2 postpartum. Her exclusively breastfed infant's growth was normal throughout the first year of life and no adverse effects were noted.
A preterm infant of 32 weeks gestation was breastfed exclusively from day 7 to day 20 postpartum. The infant's mother was taking amlodipine and labetalol in unspecified dosages for hypertension. The infant had apnea episodes unrelated to amlodipine. Growth at 2 months of age was slightly low.
Thirty-one women with pregnancy-induced hypertension postpartum received amlodipine 5 mg daily by mouth, with the dosage increased as needed to maintain blood pressure of 140/90 mm Hg or less. Their breastfed (extent not stated) infants exhibited no observed adverse cardiovascular effects within 3 weeks postpartum, although exact measurement methods were not stated.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Human adverse effects (from [3,4]): - Common side effects (incidence >1%): Peripheral edema (10–20%), headache (7%), dizziness (5%), flushing (3%); - Rare severe toxicity: Hepatitis (incidence <0.1%), hypotension (in volume-depleted patients); - No dose-dependent liver enzyme elevation (ALT/AST normal in 95% of patients at 5–10 mg daily) [3,4]
- Animal toxicity (from [4]): - Rats: 28-day oral repeat dose (1–50 mg/kg): - No mortality or overt toxicity up to 25 mg/kg; - 50 mg/kg: Mild paw edema (reversible), no histopathological changes in liver/kidney [4]; - Mice: Oral LD50 > 2000 mg/kg (single dose) [3]
- Drug-drug interactions (from [3,4]): - CYP3A4 inhibitors (e.g., ketoconazole): Increase amlodipine AUC by 2.5-fold (dose adjustment recommended); - CYP3A4 inducers (e.g., rifampicin): Decrease amlodipine AUC by 40% (may require dose increase); - No interaction with beta-blockers or diuretics [3,4]

[1]. Antitumor effects of amlodipine, a Ca2+ channel blocker, on human epidermoid carcinoma A431 cells in vitro and in vivo. Eur J Pharmacol. 2004 May 25;492(2-3):103-12.

[2]. The effects of anti-hypertensive drugs and the mechanism of hypertension in vascular smooth muscle cell-specific ATP2B1 knockout mice. Hypertens Res. 2018 Feb;41(2):80-87.

[3]. Amlodipine.

[4]. Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease [published correction appears in Drugs 1995 Nov;50(5):896]. Drugs. 1995;50(3):560-586.

Amlodipine benzenesulfonate is the benzenesulfonate salt of amlodipine. It has a role as a vasodilator agent, a calcium channel blocker and an antihypertensive agent. It contains an amlodipine.
Amlodipine Besylate is the besylate salt of amlodipine, a synthetic dihydropyridine with antihypertensive and antianginal effects. Amlodipine inhibits the influx of extracellular calcium ions into myocardial and peripheral vascular smooth muscle cells, thereby preventing vascular and myocardial contraction. This results in a dilatation of the main coronary and systemic arteries, decreased myocardial contractility, increased blood flow and oxygen delivery to the myocardial tissue, and decreased total peripheral resistance. This agent may also modulate multi-drug resistance (MDR) activity through inhibition of the p-glycoprotein efflux pump.
A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
See also: Amlodipine (has active moiety); Amlodipine besylate; benazepril hydrochloride (component of); Amlodipine besylate; telmisartan (component of) ... View More ...

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Drug Indication
Treatment of systemic arterial hypertension in cats.

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Mechanism of action (from [2,3,4]): 1. Cardiovascular effects: Amlodipine Besylate inhibits L-type calcium channel-mediated Ca²⁺ influx into VSMCs and cardiac myocytes, reducing VSMC contraction (vasodilation) and peripheral vascular resistance, thereby lowering blood pressure; in angina, it reduces myocardial oxygen demand via coronary vasodilation [2,3,4]; 2. Antitumor effects (A431 cells): Inhibits EGFR-ERK signaling pathway, induces G0/G1 arrest and apoptosis (non-cardiovascular off-target effect) [1]
- Therapeutic indications (from [3,4]): 1. Essential hypertension (monotherapy or combination with other antihypertensives); 2. Chronic stable angina; 3. Vasospastic angina (Prinzmetal’s angina) [3,4]; 4. No FDA-approved antitumor indication (preclinical data only in [1]) [1]
- FDA warning information (from [3]): - Black box warning: None; - Warnings: Use with caution in heart failure patients (may increase risk of pulmonary edema); avoid in patients with severe aortic stenosis [3]

C20H25CLN2O5.C6H6O3S

567.05

566.148

111470-99-6

Amlodipine;88150-42-9;Amlodipine maleate;88150-47-4;Amlodipine-d4 besylate;Amlodipine mesylate;246852-12-0

60496

White to off-white solid powder

1.227g/cm3

527.2ºC at 760 mmHg

199-201°C

272.6ºC

3.34E-11mmHg at 25°C

5.309

162.63

3

10

11

38

830

0

ZPBWCRDSRKPIDG-UHFFFAOYSA-N

InChI=1S/C20H25ClN2O5.C6H6O3S/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21;7-10(8,9)6-4-2-1-3-5-6/h5-8,17,23H,4,9-11,22H2,1-3H3;1-5H,(H,7,8,9)

3,5-Pyridinedicarboxylic acid, 2-((2-aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (+-)-, monobenzenesulfonate

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: ≥ 2.5 mg/mL (4.41 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (4.41 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 25.0 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: ≥ 2.5 mg/mL (4.41 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 25.0 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 4 中的溶解度: 2 mg/mL (3.53 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。