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Nimodipine Sale

(Synonyms: 尼莫地平; BAY-e 9736) 目录号 : GC16587

Nimodipine是一种1,4-二氢吡啶类L型钙离子通道拮抗剂,主要用于治疗动脉瘤性蛛网膜下腔出血(aSAH),预防脑血管痉挛。

Nimodipine Chemical Structure

Cas No.:66085-59-4

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Description

Nimodipine is a 1,4-dihydropyridine L-type calcium channel antagonist, mainly used to treat aneurysmal subarachnoid hemorrhage (aSAH) and prevent cerebral vasospasm[1]. Nimodipine can block voltage-dependent calcium channels, reduce calcium influx, protect neurons, and reduce oxidative stress and cell apoptosis[2, 3].

In vitro, pretreatment of PC12 cells with Nimodipine (20μM) for 48h significantly reduced the cytotoxic effects of EtOH and osmotic stress on cells, but had no effect on hypoxia-induced cytotoxicity[4]. Pretreatment of Schwann cells, neurons and astrocytes with Nimodipine (1, 10, 20μM) for 24h reduced the cytotoxic effects of EtOH, osmotic pressure and heat stress on cells in a dose-dependent manner[5].

In vivo, Nimodipine (5, 10, 15mg/kg) was intraperitoneally injected into rats with experimental myocardial infarction for 7 days, which improved the hemodynamic parameters of rats, reversed the histopathological and ultrastructural changes, increased endogenous antioxidants, maintained the serum levels of myocardial biomarkers CK-MB, LDH, SGOT, Trop-T and cGMP, and showed a more powerful cardioprotective effect when combined with vinpocetine[6].

References:
[1] Wiputri O I, Hidayati H B. The Role of Nimodipine as a Neurorestorative Drug in Preventing Cerebral Vasospasm Related to Subarachnoid Aneurysmal Hemorrhage[J]. Int J Pharma Res Health Sci, 2019, 7(6): 3079-83.
[2] Singh A, Verma P, Balaji G, et al. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinsonism in mice[J]. Neurochemistry international, 2016, 99: 221-232.
[3] Kusakabe M, Hasegawa Y. Nimodipine promotes neurite outgrowth and protects against neurotoxicity in PC12 cells[J]. Iranian journal of basic medical sciences, 2021, 24(1): 51.
[4] Bork K, Wurm F, Haller H, et al. Neuroprotective and neuroregenerative effects of nimodipine in a model system of neuronal differentiation and neurite outgrowth[J]. Molecules, 2015, 20(1): 1003-1013.
[5] Leisz S, Simmermacher S, Prell J, et al. Nimodipine-dependent protection of schwann cells, astrocytes and neuronal cells from osmotic, oxidative and heat stress is associated with the activation of AKT and CREB[J]. International Journal of Molecular Sciences, 2019, 20(18): 4578.
[6] Ansari M A, Iqubal A, Ekbbal R, et al. Effects of nimodipine, vinpocetine and their combination on isoproterenol-induced myocardial infarction in rats[J]. Biomedicine & Pharmacotherapy, 2019, 109: 1372-1380.

Nimodipine是一种1,4-二氢吡啶类L型钙离子通道拮抗剂,主要用于治疗动脉瘤性蛛网膜下腔出血(aSAH),预防脑血管痉挛[1]。Nimodipine能够阻断电压依赖性钙通道,减少钙离子内流,对神经元具有保护作用,还能够减轻氧化应激和细胞凋亡[2, 3]

在体外,Nimodipine(20μM)预处理PC12细胞48h,显著降低了EtOH和渗透压应激条件对细胞的细胞毒性作用,而对缺氧诱导的细胞毒性无影响[4]。Nimodipine(1, 10, 20μM)预处理Schwann细胞、神经元细胞和星形胶质细胞24h,以剂量依赖性方式降低了EtOH、渗透压和热应激条件对细胞的细胞毒性作用[5]

在体内,Nimodipine(5, 10, 15mg/kg)通过腹腔注射治疗实验性心肌梗死大鼠7天,改善了大鼠血液动力学参数,逆转了组织病理学和超微结构的变化,增加了内源性抗氧化剂,维持了心肌生物标志物CK-MB、LDH、SGOT、Trop-T和cGMP的血清水平,且与Vinpocetine联合用药表现出了更强大的心脏保护作用[6]

实验参考方法

Cell experiment [1]:

Cell lines

PC12 cells

Preparation Method

Cells were seed on Collagen IV coated plates and allowed to attach for 24h. Afterwards cells were pretreated with 20μM Nimodipine or DMSO for 48h. Alcohol stress: Medium was changed and cells were treated with 200mM EtOH and 20µM Nimodipine or DMSO and incubated for 48h. Osmotic stress: Medium was changed and cells were treated with additional NaCl to increase the osmotic concentration from 290 to 450mosmol/L and 20µM Nimodipine or DMSO and incubated for 48h.

Reaction Conditions

20μM; 48h

Applications

Cytotoxicity of 200mM EtOH and osmotic stress (450mosmol/L) was significantly reduced with Nimodipine pretreatment, while Nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells.

Animal experiment [2]:

Animal models

Wistar albino rats

Preparation Method

Rats were randomly divided into Group I-Vehicle Control Group; Group II-Toxic control (ISO 85mg/kg, i.p.); Group III, IV and V-Nimodipine (5, 10 and 15mg/kg, i.p. respectively) with ISO; Group VI-Nimodipine (15mg/kg) alone; Group VII–Nimodipine+Vinpocetine (10mg/kg+10mg/kg) with ISO; Group VIII-Nimodipine+Vinpocetine (10mg/kg+10mg/kg) alone; Group IX-Diltiazem (25mg/kg, p.o) with ISO; Group X-Diltiazem (25mg/kg) alone and Group XI-Vinpocetine (10mg/kg, p.o.) with ISO for 7 days. After 24h of the last dose, haemodynamics were assessed then animals were sacrificed and biochemical, histopathological and ultrastructural changes were measured.

Dosage form

5, 10, 15mg/kg; 7 days; i.p.

Applications

Combination of Nimodipine with Vinpocetine exhibit strong cardioprotective effect. This combination improved haemodynamic parameters, reversed changes at the histopathological and ultrastructural level, increased endogenous antioxidants and maintained the serum levels of cardiac biomarkers CK-MB, LDH, SGOT, Trop-T and cGMP.

References:
[1] Bork K, Wurm F, Haller H, et al. Neuroprotective and neuroregenerative effects of nimodipine in a model system of neuronal differentiation and neurite outgrowth[J]. Molecules, 2015, 20(1): 1003-1013.
[2]Ansari M A, Iqubal A, Ekbbal R, et al. Effects of nimodipine, vinpocetine and their combination on isoproterenol-induced myocardial infarction in rats[J]. Biomedicine & Pharmacotherapy, 2019, 109: 1372-1380.

化学性质

Cas No. 66085-59-4 SDF
别名 尼莫地平; BAY-e 9736
化学名 3-O-(2-methoxyethyl) 5-O-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Canonical SMILES CC1=C(C(C(=C(N1)C)C(=O)OC(C)C)C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OCCOC
分子式 C21H26N2O7 分子量 418.45
溶解度 ≥ 108mg/mL in DMSO, ≥ 41.8mg/mL in EtOH 储存条件 Store at -20°C,protect from light
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储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
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1 mg 5 mg 10 mg
1 mM 2.3898 mL 11.9489 mL 23.8977 mL
5 mM 0.478 mL 2.3898 mL 4.7795 mL
10 mM 0.239 mL 1.1949 mL 2.3898 mL
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