Aranidipine   中文名称: 阿雷地平

一种用于自发性高血压大鼠的新型 Ca2+ 通道拮抗剂是 aranidipine (MPC-1304)。给自发性高血压大鼠（SHR）口服剂量为 3 和 10 mg/kg 的阿拉地平后，与心肌结合的特异性 [3H](+)-PN 200-110 的 Bmax 值显着增加。对照组。来减少数值。与对照值相比，1小时（3 mg/kg）、1小时和6小时（10 mg/kg）的Bmax值显着降低（分别为47.7%、48.9%和25.8%）。效果在一小时后达到顶峰并逐渐减弱。口服阿兰地平6小时（3mg/kg）和12或24小时（10mg/kg）后的Bmax值与对照值没有显示出显着差异，表明阿兰地平作用不再存在。口服阿兰地平不影响心肌[3H](+)-PN 200-110 结合的Kd 值[1]。

Absorption, Distribution and Excretion
After administration, aranidipine is rapidly absorbed from the gastrointestinal tract. After absorption, the AUC and Cmax increased linearly in a dose-dependent manner, the Cmax was attained in approximate 3.8-4.8 hours for aranidipine and 4.8-6 hours for the metabolite M-1. The bioavailability of aranidipine in rat, dog, and monkey was about 48%, 41% and 3% respectively.
Unchanged aranidipine is found in plasma but not in the urine after 1 hour of administration. Just a small amount of drug was found in the bile. These results indicate that the excretion profile of aranidipine is mainly driven by metabolism and not by excretion. When including the metabolites, 52-56% of the original dose is disposed in the urine, 34-45% in feces and 3-4% in expired air. The excretion in the bile was 59% of the administered dose and 63% of this portion is reabsorbed.

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Metabolism / Metabolites
Eight metabolites of aranidipine were found after oral administration. These metabolites were brought by a reduction of the ketone group, oxidation of dihydropyridine ring and de-esterification at the C-3 position.

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Biological Half-Life
The elimination half-life of aranidipine and the M-1 metabolite are 1.1-1.2 hour and 2.7-3.5 hour respectively.

Protein Binding
The binding ratio of plasma proteins of aranidipine varies from 84-95%. This ratio of the drug is similar to the unchanged form and for the M-1 metabolite. Most of the binding happens towards serum albumin and a lower amount corresponds to the alpha1-acid glycoprotein.

[1]. Receptor occupation and pharmacokinetics of MPC-1304, a new Ca2+ channel antagonist, in spontaneously hypertensive rats. Eur J Pharmacol. 1995 Dec 12;287(2):191-6.

Aranidipine is an organic molecular entity.
Aranidipine is a novel dihydropyridine derivative that gives rise to two active metabolites (M-1α and M-1β) that exhibit hypotensive activity. It is a calcium antagonist with the formula methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate. It was developed by Maruko Seiyaku, introduced by Taiho and launched in Japan in 1997.

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Drug Indication
Aranidipine has been used for many years to treat angina pectoris and hypertension.

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Mechanism of Action
The high potential of aranidipine is thought to be related to the additional calcium antagonistic activity of its metabolite. The mechanism is thought to be related to the capacity of aranidipine and its metabolites to vasodilate afferent and efferent arterioles. this action is performed through the inhibition of voltage-dependent calcium channels. The typical mechanism of action of aranidipine, as all dihydropyridines, is based on the inhibition of L-type calcium channels, decreasing calcium concentration and inducing smooth muscle relaxation. It is a selective alpha2-adrenoreceptor antagonist which inhibits vasoconstrictive responses.

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Pharmacodynamics
Pre-clinical studies with aranidipine and its two metabolites have shown production of increases in femoral blood flow. It has been shown to present potent and long-lasting vasodilating actions. Aranidipine and its metabolites are shown to inhibit calcium-induced contraction in isolated rabbit arteries. Studies have shown that aranidipine is more potent to reduce blood pressure than other dihydropyridines. Aranidipine produce changes in renal blood flow, this effect may be explained by its effect on alpha-2-adrenoreceptor-mediated vasoconstriction.

C19H20N2O7

388.38

388.127

86780-90-7

2225

Light yellow to yellow solid powder

1.284 g/cm3

530ºC at 760 mmHg

155°

274.3ºC

1.555

2.986

127.52

1

8

7

28

748

0

NCUCGYYHUFIYNU-UHFFFAOYSA-N

InChI=1S/C19H20N2O7/c1-10(22)9-28-19(24)16-12(3)20-11(2)15(18(23)27-4)17(16)13-7-5-6-8-14(13)21(25)26/h5-8,17,20H,9H2,1-4H3

3-O-methyl 5-O-(2-oxopropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Aranidipine MPC 1304 MPC-1304 MPC1304CCRIS 6724 CCRIS-6724 CCRIS6724

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 该产品在溶液状态不稳定，请现配现用。

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

DMSO : ~125 mg/mL (~321.86 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (5.36 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 20.8 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: ≥ 2.08 mg/mL (5.36 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 20.8 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: ≥ 2.08 mg/mL (5.36 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 20.8 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。