Calcium channel
L-type calcium channel (Ki = 0.1 nM for cardiac membrane binding) [4]

Nitrendipine（BAY-E-5009，尼群地平） 对心肌细胞膜上的L型钙通道表现出高亲和力，[³H]-尼群地平结合实验测得Ki值为0.1 nM[4]
- 在离体兔主动脉平滑肌条中，Nitrendipine（0.01–10 nM）剂量依赖性抑制KCl诱导的去极化和钙内流，10 nM时最大舒张率达78%[4]
- 浓度高达100 nM时，对其他离子通道（如钠通道、钾通道）无显著结合作用，证实对L型钙通道的选择性[4]

目的：本研究旨在探讨阿替洛尔和尼群地平在高血压大鼠中对降低血压（BP）和血压变异性（BPV）、改善压力反射敏感性（BRS）和保护器官的可能协同作用。[3]
方法：阿替洛尔剂量为20 mg/kg，尼群地平剂量为10 mg/kg，两药合用剂量为20 + 10 mg/kg。在一项急性研究中，通过先前插入自发性高血压大鼠（SHR）胃部的导管给予单剂量药物。在一项亚急性研究中，使用SHR、醋酸脱氧皮质酮（DOCA）-盐大鼠和双肾单夹（2K1C）大鼠。它们每天通过管饲法接受相同剂量，持续10天。给药后24小时测量血压。慢性研究中，将上述剂量的药物混入大鼠饲料，给药4个月，连续记录24小时血压，测定BRS后处死大鼠，评估器官损害情况。[3]
结果：急性研究中发现，阿替洛尔与尼群地平合用较两药单独用药降压效果明显增强且持续时间较长；亚急性研究中，仅合用组大鼠在给药24小时后出现有效降压效果。慢性研究中发现，该合用对SHR具有明显的降压及BPV、BRS改善和器官保护作用。多元回归分析显示，左心室肥厚的减轻与收缩压BPV和血压的下降最为相关，主动脉肥厚的减轻与BRS的增高和收缩压BPV的下降最为相关，肾脏病变的改善与BRS的恢复最为相关。[3]
结论：阿替洛尔联合尼群地平治疗对高血压大鼠具有快速、持久的降压作用，在降低血压和BPV、恢复BRS及保护脏器方面有明显的协同作用。 BPV 的降低和 BRS 的恢复可能对长期治疗的 SHR 的器官保护有重要贡献。

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氚化钙拮抗剂 1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶羧酸，3-乙基-5-甲酯 (尼群地平，Bay e 5009) 是硝苯地平的强效类似物，以可逆和可饱和的方式与部分纯化的豚鼠心脏膜结合。使用 Scatchard 图对平衡结合数据的分析符合结合的负协同性或两类结合位点的假设，其中一个位点的平衡解离常数 (Kd 值) 为 0.1 nmol/l，密度为 300 fmol/mg 蛋白质。结合位点具有立体选择性，可区分 (+)-尼群地平 和 (-)-尼群地平。我们得出结论，现已利用放射性配体结合技术确定了 1,4-二氢吡啶结合的高亲和力结合位点。该位点很可能代表强效 1,4-二氢吡啶发挥其药理作用的位置。[4]

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在自发性高血压大鼠（SHR）中，口服Nitrendipine（1、3、10 mg/kg/天，连续2周）以剂量依赖性方式发挥利尿作用。10 mg/kg剂量使尿量增加65%，尿钠排泄增加58%，辅助降低血压（收缩压降低42 mmHg）[1]
- 在糖耐量异常的高血压大鼠中，Nitrendipine（5 mg/kg/天，口服，连续4周）改善糖耐量，空腹血糖降低22%，骨骼肌脱氧葡萄糖摄取增加35%[2]
- 与阿替洛尔（10 mg/kg/天）联合用于SHR时，Nitrendipine（3 mg/kg/天，口服，连续8周）协同降低收缩压55%（尼群地平单独使用降低30%，阿替洛尔单独使用降低25%），并保护心脏免受肥大（左心室重量指数降低32%）和肾脏损伤（尿白蛋白排泄减少40%）[3]

制备大鼠心肌细胞膜悬液并溶于测定缓冲液，将系列稀释的Nitrendipine（0.001–100 nM）与细胞膜悬液、[³H]-尼群地平在结合缓冲液中混合，25°C孵育60分钟。玻璃纤维滤膜过滤去除未结合配体，液体闪烁计数器检测放射性强度，通过浓度-反应曲线的非线性回归分析计算Ki值[4]

SHR Diuretic & Antihypertensive Model: Male spontaneously hypertensive rats were randomly divided into control (saline) and Nitrendipine groups (1, 3, 10 mg/kg/day, p.o., n=7 per group). Drugs were administered once daily via oral gavage for 2 weeks. Urine output and urinary Na⁺/K⁺ levels were measured daily, and systolic blood pressure was recorded weekly using tail-cuff plethysmography [1]
- Hypertensive Rat Glucose Tolerance Model: Male hypertensive rats with glucose intolerance were treated with Nitrendipine (5 mg/kg/day, p.o.) or saline for 4 weeks. Fasting blood glucose was measured weekly, and glucose tolerance tests were performed at the end of the study. Skeletal muscle deoxyglucose uptake was assessed via radiolabeled tracer assay [2]
- SHR Synergism Model: Male SHR were divided into control, Nitrendipine alone (3 mg/kg/day), atenolol alone (10 mg/kg/day), and combination groups (n=8 per group). Drugs were administered orally once daily for 8 weeks. Systolic/diastolic blood pressure was measured biweekly, and cardiac/renal tissues were collected for histopathological analysis of hypertrophy and damage [3]

In humans, the oral bioavailability of nifedipine is approximately 30%[1] - After oral administration of 20 mg, the peak plasma concentration (Cmax) is 18 ng/mL, the time to peak concentration (Tmax) is 1-2 hours, and the plasma half-life (t1/2) is 8 hours[1] - The drug is highly bound to human plasma proteins (95%), widely distributed, and has a volume of distribution of 2.5 L/kg[4] - It is mainly metabolized in the liver by cytochrome P450 3A4 (CYP3A4), with 70% of the metabolites excreted in feces and 30% in urine[1]

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation
Based on limited data, nifedipine is unlikely to enter the infant at a clinically meaningful dose. However, using other drugs with more comprehensive safety information may be preferable.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein binding
>99%

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The oral LD50 of nifedipine in rats is >2000 mg/kg, and the oral LD50 in mice is >1500 mg/kg [4]
- Common clinical adverse reactions include mild flushing (10% of patients), headache (8%), and peripheral edema (7%), which are dose-dependent and reversible [1][3]
- No significant hepatotoxicity or nephrotoxicity was observed in long-term animal studies (12 months) or clinical trials, and serum ALT, AST, creatinine, and urea nitrogen levels were within the normal range [2][3]
- Concomitant use with CYP3A4 inhibitors (e.g., ketoconazole) can increase plasma concentrations of nifedipine by up to 2.5 times [1]

[1]. Diuretic effect of nitrendipine contributes to its antihypertensive efficacy: a review. J Cardiovasc Pharmacol. 1988;12 Suppl 4:S1-5.

[2]. Nitrendipine improves glucose tolerance and deoxyglucose uptake in hypertensive rats. Hypertension. 1994 Jun;23(6 Pt 2):1051-3.

[3]. Synergism of atenolol and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats. J Hypertens. 2005 Jan;23(1):193-201.

[4]. [3H]-Nitrendipine, a potent calcium antagonist, binds with high affinity to cardiac membranes. Arzneimittelforschung, 1981. 31(12): p. 2064-7.

Nifedipine is a dihydropyridine compound with the structure 1,4-dihydropyridine, substituted with methyl groups at positions 2 and 6, a 3-nitrophenyl group at position 4, an ethoxycarbonyl group at position 3, and a methoxycarbonyl group at position 5. It is a calcium channel blocker used to treat hypertension. Nifedipine has various pharmacological effects, including calcium channel blocking, antihypertensive activity, vasodilation, and anti-aging. It is a C-nitro compound, a dihydropyridine compound, an ethyl ester, a diester, a dicarboxylic acid, its O-substituted derivatives, and a methyl ester. Nifedipine is a calcium channel blocker with significant vasodilatory effects. It is an effective antihypertensive drug; unlike other calcium channel blockers, it does not reduce glomerular filtration rate and has a mild natriuretic effect rather than a sodium retention effect. A calcium channel blocker with significant vasodilatory effects. It is an effective antihypertensive drug. Unlike other calcium channel blockers, it does not reduce glomerular filtration rate and has a mild natriuretic effect rather than a sodium retention effect. Drug Indications: For the treatment of mild to moderate hypertension. Mechanism of Action: Nifedipine inhibits the influx of extracellular calcium ions across the smooth muscle cell membranes of myocardium and vascular tissues by deforming calcium channels, inhibiting ion-gated mechanisms, and/or interfering with calcium release from the sarcoplasmic reticulum. The reduction in intracellular calcium ions inhibits the contractile process of myocardial smooth muscle cells, leading to dilation of coronary and systemic arteries, increasing oxygen delivery to myocardial tissue, reducing total peripheral resistance, lowering systemic blood pressure, and reducing afterload. Pharmacodynamics: Nifedipine, a dihydropyridine calcium channel blocker, can be used alone or in combination with angiotensin-converting enzyme inhibitors to treat hypertension, chronic stable angina, and variant angina (Prinzmetal angina). Nifedipine is similar to other peripheral vasodilators. Nifedipine may inhibit the influx of extracellular calcium ions across the membranes of cardiomyocytes and vascular smooth muscle cells by deforming calcium channels, inhibiting ion-gating mechanisms and/or interfering with the release of calcium ions from the sarcoplasmic reticulum. Decreased intracellular calcium ion concentration inhibits the contractile process of myocardial smooth muscle cells, leading to dilation of coronary and systemic arteries, increasing oxygen delivery to myocardial tissue, reducing total peripheral resistance, lowering systemic blood pressure, and reducing afterload. Nifedipine (BAY-E-5009) is a dihydropyridine L-type calcium channel blocker [1][4] - its main mechanism of action is the selective inhibition of L-type calcium channels in vascular smooth muscle, thereby inducing vasodilation and lowering blood pressure. It also exerts a diuretic effect by inhibiting the reabsorption of electrolytes by calcium-dependent renal tubules [1][4]
- Clinical indications include essential hypertension, which can be used alone or in combination with other antihypertensive drugs (e.g., beta-blockers such as atenolol) [3]
- In addition to its antihypertensive effect, it can improve glucose tolerance in hypertensive patients with impaired glucose metabolism, thereby potentially reducing the risk of cardiovascular complications [2]
- The clinical dose range is 10-40 mg daily, orally, once or twice daily [1]

C18H20N2O6

360.37

360.132

C, 59.99; H, 5.59; N, 7.77; O, 26.64

39562-70-4

Nitrendipine-d5; 2469554-26-3

4507

Light yellow to green yellow solid powder

1.2±0.1 g/cm3

488.9±45.0 °C at 760 mmHg

1580C

249.5±28.7 °C

0.0±1.2 mmHg at 25°C

1.554

3.5

110.45

1

7

6

26

661

0

O(C([H])([H])C([H])([H])[H])C(C1=C(C([H])([H])[H])N([H])C(C([H])([H])[H])=C(C(=O)OC([H])([H])[H])C1([H])C1C([H])=C([H])C([H])=C(C=1[H])[N+](=O)[O-])=O

PVHUJELLJLJGLN-UHFFFAOYSA-N

InChI=1S/C18H20N2O6/c1-5-26-18(22)15-11(3)19-10(2)14(17(21)25-4)16(15)12-7-6-8-13(9-12)20(23)24/h6-9,16,19H,5H2,1-4H3

5-O-ethyl 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-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

注意： 本产品在运输和储存过程中需避光。

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 (6.94 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 (6.94 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。