Isradipine (PN 200-110)   中文名称: 伊拉地平

伊拉地平具有良好的脑生物利用度和对 Cav1.3 通道显着更高（>40 倍）的亲和力。伊拉地平在 Cav1.2 和 Cav1.3 通道上的功效几乎相同[1]。

伊拉地平（0.1~3 mg/kg；口服）以剂量依赖性方式增加钠排泄[3]。伊拉地平预处理可降低 6-羟基多巴胺诱导的神经毒性的纹状体水平。根据六只小鼠的数据，伊拉地平在纹状体水平上具有剂量依赖性保护作用。 6-羟基多巴胺诱导的变性后，伊拉地平预处理可增加存活 SNc DA 细胞的数量。当纹状体内注射 6-羟基多巴胺作为一种缓慢、进行性的损伤时，伊拉地平可以保护 SNc 多巴胺能细胞体和纹状体多巴胺能末梢免受其影响[1]。

Animal/Disease Models: Rats[3]
Doses: 0.1~3 mg/kg
Route of Administration: Po
Experimental Results: Sodium excretion increased in a dose-dependent manner.

Absorption, Distribution and Excretion
Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.
Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.

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Metabolism / Metabolites
Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.

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Biological Half-Life
8 hours

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because no information is available on the use of isradipine during breastfeeding, an alternate drug may be preferred.
◉ 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
95%

[1]. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease. Neurobiol Dis. 2011;43(2):364-371.

[2]. Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats. Exp Neurol. 1997;148(1):45-50.

[3]. Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart. Am J Cardiol. 1987;59(3):30B-36B.

Isradipine is an isopropyl ester, a methyl ester, a dihydropyridine and a benzoxadiazole.
Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.
Isradipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of isradipine is as a Calcium Channel Antagonist.
Isradipine is a second generation calcium channel blocker that is used to treat hypertension. Isradipine is associated with a low rate of serum enzyme elevations during therapy, but has not been linked convincingly to instances of clinically apparent liver injury.
Isradipine is a dihydropyridine calcium channel blockers with antihypertensive and vasodilator activities. Isradipine blocks the calcium entry through the calcium ion channels of coronary and peripheral vascular smooth muscle, thereby dilating coronary arteries and peripheral arterioles. This increases oxygen delivery due to an increased blood flow and reduces oxygen requirements due to decrease in total peripheral resistance. (NCI05)
A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.

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Drug Indication
For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.

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Mechanism of Action
Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

C19H21N3O5

371.39

371.148

75695-93-1

3784

Light yellow to yellow solid powder

1.3±0.1 g/cm3

501.9±60.0 °C at 760 mmHg

166-168°C

257.4±32.9 °C

0.0±1.3 mmHg at 25°C

1.566

3.59

103.55

1

8

6

27

685

0

HMJIYCCIJYRONP-UHFFFAOYSA-N

InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3

3-O-methyl 5-O-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-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 (6.73 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 (6.73 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 (6.73 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 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 2% DMSO +Corn oil : 10mg/mL

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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。