拉西地平（0.01-100 μM；24 小时）在体外以浓度依赖性方式抑制 HKC 增殖[1]。通过控制 caspase-3 通路，拉西地平（0.01-100 μM；24 小时）可保护 HKC 免受 ATP 耗竭和恢复引起的细胞凋亡[1]。

在 apoE 缺陷动物中，拉西地平（0.3、1.0、3.0 mg/kg；口服；每日一次，持续 10 周）可降低血浆内皮素浓度，并具有抗动脉粥样硬化特性[2]。

细胞增殖测定[1]
细胞类型： HKC 细胞
测试浓度： 0.01-100 μM
孵育时间： > 24 小时
实验结果：以浓度依赖性方式证明抗增殖活性。

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细胞凋亡分析[1]
细胞类型： HKC 细胞（肾缺血再灌注 (I/R) 模型）
测试浓度： 1, 10 μM
孵育时间： 24 h
实验结果： AA诱导HKC细胞凋亡，早期凋亡细胞比例分别为1.47%和0.30分别为 1 和 10 μM 剂量的％。

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蛋白质印迹分析[1]
细胞类型： HKC 细胞（肾缺血再灌注 (I/R) 模型）
测试浓度： > 1, 10 μM
孵育时间： 24 小时（预处理）
实验结果： ATP 耗尽和恢复后受损细胞的细胞色素 c 表达减少。显着增加 Bcl-2 蛋白的表达，但减少 Bax 蛋白的表达。

Animal/Disease Models: Female C57BL/6 mice (Homozygous ; apoE-deficient; atherosclerosis model)[2].
Doses: 0.3, 1.0, 3.0 mg/kg
Route of Administration: po (oral gavage); single daily for 10 weeks.
Experimental Results: Induced a significant dose-dependent decrease in plasma endothelin levels. Dramatically decreased the mean lesion area in a dose-related manner by 10, 17 and 53% for 0.3, 1.0, 3.0 mg/kg, respectively.

Absorption, Distribution and Excretion
Since it is a highly lipophilic compound, lacidpine is rapidly absorbed from the gastrointestinal tract following oral administration with the peak plasma concentrations reached between 30 and 150 minutes of dosing. The peak plasma concentrations display large interindividual variability, with the values ranging from 1.6 to 5.7 μg/L following single-dose oral administration of lacidipine 4mg in healthy young volunteers. Absolute bioavailability is less than 10% due to extensive first-pass metabolism in the liver.
Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine.

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Metabolism / Metabolites
Lacidipine undergoes complete CYP3A4-mediated hepatic metabolism, with no parent drug detected in the urine or faeces. The 2 main metabolites have no pharmacological activity.

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Biological Half-Life
The average terminal half-life of lacidipine ranges from between 13 and 19 hours at steady state.

Protein Binding
Lacidipine is highly protein-bound (more than 95%) to predominantly albumin and to a lesser extent, alpha-1-glycoprotein.

[1]. Lacidipine attenuates apoptosis via a caspase-3 dependent pathway in human kidney cells. Cell Physiol Biochem. 2013;32(4):1040-9.

[2]. The calcium-channel blocker lacidipine reduces the development of atherosclerotic lesions in the apoE-deficient mouse. J Hypertens. 2000 Oct;18(10):1429-36.

Lacidipine is a cinnamate ester and a tert-butyl ester.
Lacidipine is a lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity. Due to its long duration of action, lacidipine does not lead to reflex tachycardia. It displays specificity in the vascular smooth muscle, where it acts as an antihypertensive agent to dilate peripheral arterioles and reduce blood pressure. Compared to other dihydropyridine calcium antagonists, lacidipine exhibits a greater antioxidant activity which may confer potentially beneficial antiatherosclerotic effects. Lacidipine is a highly lipophilic molecule that interacts with the biological membranes. Through radiotracer analysis, it was determined that lacidipine displays a high membrane partition coefficient leading to accumulation of the drug in the membrane and slow rate of membrane washout. When visualized by small-angle X-ray diffraction with angstrom resolution to examine its location within the membranes, lacidipine was found deep within the membrane's hydrocarbon core. These results may explain the long clinical half-life of lacidipine. In randomised, well-controlled trials, administration of daily single-dose lacidipine ranging from 2-6 mg demonstrated comparable antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). It is available as once-daily oral tablets containing 2 or 4 mg of the active compound commonly marketed as Lacipil or Motens. It is not currently FDA-approved.

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Drug Indication
Indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including β-adrenoceptor antagonists, diuretics, and ACE-inhibitors.

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Mechanism of Action
By blocking the voltage-dependent L-type calcium channels, it prevents the transmembrane calcium influx. Normally, calcium ions serve as intracellular messengers or activators in exictable cells including vascular smooth muscles. The influx of calcium ultimately causes the excitation and depolarization of the tissues. Lacidipine inhibits the contractile function in the vascular smooth muscle and reduce blood pressure. Due to its high membrane partition coefficient, some studies suggest that lacidipine may reach the receptor via a two-step process; it first binds and accumulates in the membrane lipid bilayer and then diffuses within the membrane to the calcium channel receptor. It is proposed that lacidipine preferentially blocks the inactivated state of the calcium channel. Through its antioxidant properties shared amongst other dihydropyridine calcium channel blockers, lacidipine demonstrates an additional clinical benefit. Its antiatherosclerotic effects are mediated by suppressing the formation of reactive oxygen species (ROS) and subsequent inflammatory actions by chemokines, cytokines and adhesion molecules, thus reducing atherosclerotic lesion formation. Lacidipine may also suppress cell proliferation and migration in smooth muscle cells and suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques.

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Pharmacodynamics
acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure. Following the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers).

C26H33NO6

455.54

455.23

103890-78-4

Lacidipine-13C8;1261432-01-2

5311217

White to off-white solid powder

1.1±0.1 g/cm3

558.4±50.0 °C at 760 mmHg

174-175°C

291.5±30.1 °C

0.0±1.5 mmHg at 25°C

1.540

5.49

90.93

1

7

11

33

805

0

CCOC(=O)C1=C(NC(=C(C1C2=CC=CC=C2/C=C/C(=O)OC(C)(C)C)C(=O)OCC)C)C

GKQPCPXONLDCMU-CCEZHUSRSA-N

InChI=1S/C26H33NO6/c1-8-31-24(29)21-16(3)27-17(4)22(25(30)32-9-2)23(21)19-13-11-10-12-18(19)14-15-20(28)33-26(5,6)7/h10-15,23,27H,8-9H2,1-7H3/b15-14+

diethyl 2,6-dimethyl-4-[2-[(E)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylate

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: ≥ 2.5 mg/mL (5.49 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 (5.49 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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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。