Verapamil
(Synonyms: 维拉帕米; (±)-Verapamil; CP-16533-1) 目录号 : GC61811
Verapamil是 L 型钙通道阻滞剂和肾上腺素能受体拮抗剂，常用于高血压、心律失常和心绞痛的研究。
Cas No.:52-53-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
Cell lines | SHSY5Y cells |
Preparation Method | SHSY5Y cells were seeded into 24-well plates . 2% FBS medium containing Verapamil at a concentration range from 1nM to 0.5mM was added to the cells for 1, 6, 24 and 48h. Cell viability was assessed using the MTT reduction assay. |
Reaction Conditions | Verapamil: 1nM -0.5mM; 6, 24 and 348h. |
Applications | A highly statistical reduction in cell viability was observed under 0.5mM Verapamil treatment and was still not recovered after 48h; the other tested concentrations failed to produce any significant effects after 1, 6, and 24h. |
| Animal experiment [2]: | |
Animal models | Myotonic dystrophy mouse model |
Preparation Method | Mice were provided Verapamil via ingestion of Nutra-Gel Complete Nutrition food to a final dose of 200mg/kg/day Verapamil. Mice that did not receive verapamil, were provided Nutra-Gel Complete Nutrition food that had 1mL ddH2O added to serve as a vehicle control. |
Dosage form | Verapamil (200mg/kg; po; 10weeks) |
Applications | Long-term administration of the calcium channel blocker Verapamilto mice rescued the life of mice with myotonic dystrophy type 1 and improved force production, muscle stiffness, and respiratory function. |
References: | |
Verapamil is an L-type calcium channel blocker and adrenergic receptor antagonist commonly used in studies of hypertension, arrhythmias and angina pectoris[1].
Verapamil (5µM-5mM; 1h) affects human erythrocytes, where the normal disc-like shape of the erythrocytes changes to oropharyngeal cysts, small cells, spherical oropharyngeal cysts and haemolysis occurs at a concentration of Verapamil of 5mM. As the concentration of Verapamil was increased from 5µM, the morphology of the erythrocytes changed [2].The survival and proliferation rates of PC-3, A549, and COLO 205 cells were decreased after treatment with Verapamil (50–200μM; 6–48h)[3] .
In the neuroinflammatory model, pretreatment with Verapamil (10mg/kg; ip; 7days) in the morning reduced CD11b+, CD68+ and Iba1 by 54.33%, 24.68% and 41.33%, respectively. The above markers were also reduced in evening pretreated mice by 41.01%, 18.3% and 24.06%, respectively [4].Long-term administration of Verapamil (200mg/kg; po; 10weeks) to mice rescued the lives of mice with myotonic dystrophy type 1 and improved myogenesis, muscle stiffness and respiratory function [5].Verapamil (1.0, 2.5, 5.0 and 10mg/kg; ip; 48h) impaired memory consolidation in a parameter- and dose-dependent manner in an absent-field habituation task in rats [6].
References:
[1] Kania E, Pająk B, O'Prey J, Sierra Gonzalez P, Litwiniuk A, Urbańska K, Ryan KM, Orzechowski A. Verapamil treatment induces cytoprotective autophagy by modulating cellular metabolism. FEBS J. 2017 May;284(9):1370-1387.
[2] Suwalsky M, Munoz M, Mennickent S, et al. Structural effects of verapamil on cell membranes and molecular models[J]. Journal of the Chilean Chemical Society, 2010, 55(1): 1-4.
[3] Mosalam EM, Elberri AI, Sallam AS, Salem HR, Metwally EM, Abdallah MS, Shaldam MA, Mansour HEA. Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes. Mol Med. 2022 Nov 26;28(1):139.
[4] Rattis BAC, Freitas AC, Oliveira JF, Calandrini-Lima JLA, Figueiredo MJ, Soave DF, Ramos SG, Celes MRN. Effect of Verapamil, an L-Type Calcium Channel Inhibitor, on Caveolin-3 Expression in Septic Mouse Hearts. Oxid Med Cell Longev. 2021 Apr 8;2021:6667074.
[5]Cisco LA, Sipple MT, Edwards KM, Thornton CA, Lueck JD. Verapamil mitigates chloride and calcium bi-channelopathy in a myotonic dystrophy mouse model. J Clin Invest. 2024 Jan 2;134(1):e173576.
[6]Popović N, Giménez de Béjar V, Caballero-Bleda M, Popović M. Verapamil Parameter- and Dose-Dependently Impairs Memory Consolidation in Open Field Habituation Task in Rats. Front Pharmacol. 2017 Jan 10;7:539.
Verapamil是 L 型钙通道阻滞剂和肾上腺素能受体拮抗剂，常用于高血压、心律失常和心绞痛的研究[1]。
Verapamil （5µM-5mM；1h）影响人红细胞，在在 5mM 浓度的Verapamil下，红细胞的正常圆盘状形状变为口咽囊肿、小细胞、球形口咽囊肿，并发生溶血。随着Verapamil浓度从 5µM 增加，红细胞的形态发生变化 [2]。PC-3、A549 和 COLO 205 细胞存活率和增殖率在Verapamil（50–200μM；6–48h）处理后降低 [3] 。
在神经炎症模型中，早晨给予Verapamil (10mg/kg；ip ；7天 ) 预处理分别使 CD11b+、CD68+ 和 Iba1 降低 54.33%、24.68% 和 41.33%，晚上预处理小鼠的以上标志物也有降低，分别降低了 41.01%、18.3% 和 24.06%[4]。小鼠长期服用Verapamil（200mg/kg； po； 10weeks）能挽救1型肌营养不良症小鼠的生命，并改善肌力生成、肌肉僵硬度和呼吸功能[5]。Verapamil (1.0、2.5、5.0和10 mg/kg；ip；48h)在大鼠的旷场习惯任务中以参数和剂量依赖性的方式损害记忆巩固[6]。
| Cas No. | 52-53-9 | SDF | |
| 别名 | 维拉帕米; (±)-Verapamil; CP-16533-1 | ||
| Canonical SMILES | COC1=CC=C(C(C#N)(C(C)C)CCCN(CCC2=CC=C(OC)C(OC)=C2)C)C=C1OC | ||
| 分子式 | C27H38N2O4 | 分子量 | 454.6 |
| 溶解度 | DMSO: 100 mg/mL (219.97 mM) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 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。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1997 mL | 10.9987 mL | 21.9974 mL |
| 5 mM | 0.4399 mL | 2.1997 mL | 4.3995 mL |
| 10 mM | 0.22 mL | 1.0999 mL | 2.1997 mL |
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动物数量 | 只 |
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Verapamil in arrhythmia
Br J Clin Pharmacol 1986;21 Suppl 2(Suppl 2):183S-189S.PMID:3530300DOI:10.1111/j.1365-2125.1986.tb02869.x.
The antiarrhythmic effects of Verapamil were observed before it was appreciated that it was a calcium ion-antagonist. Intravenous Verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone. It consistently slows and regularises the ventricular response in atrial fibrillation, and usually increases the degree of AV-nodal block in atrial flutter though it occasionally induces a return to sinus rhythm. Given orally it is useful for the prophylaxis of atrioventricular reentry tachycardia, and also in modulating the atrioventricular nodal response in atrial fibrillation. Favourable response in ventricular tachycardia is exceptional and then seen in specific benign varieties. Verapamil is the agent of choice for the termination of paroxysmal supraventricular tachycardia.
How CaV1.2-bound Verapamil blocks Ca2+ influx into cardiomyocyte: Atomic level views
Pharmacol Res 2019 Jan;139:153-157.PMID:30447294DOI:10.1016/j.phrs.2018.11.017.
The first clinically used antiarrhythmic, antianginal and anti-hypertensive phenylalkylamine, Verapamil's cardiovascular activity is inextricably linked to its ability to antagonize Ca2+ overload via blocking CaV1.2, a cardiac L-type Ca2+ channel of undisputed physiological and pharmacological importance in cardiovascular disorders such as myocardial ischemia-reperfusion injury. From a structural point of view, however, the action mechanism of Verapamil is still elusive. Therefore, incorporating previous findings for Verapamil and CaV1.2, this review article puts forward two experimental data-derived and -supported 3D structure models for CaV1.2's α1 subunit and its verapamil-bound form. Furthermore, this article suggests three biophysical mechanisms, namely competitive binding, steric hindrance and electrostatic repulsion, towards an atomic level understanding of how Verapamil blocks the L-type Ca2+ current mediated by CaV1.2 in reality, which can be useful for the design and development of next-generation Ca2+ antagonists to provide safer and more effective treatment of cardiovascular diseases.
Exploratory study reveals far reaching systemic and cellular effects of Verapamil treatment in subjects with type 1 diabetes
Nat Commun 2022 Mar 3;13(1):1159.PMID:35241690DOI:10.1038/s41467-022-28826-3.
Currently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that oral Verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, our global T1D serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by Verapamil and as a potential therapeutic marker and revealed that Verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirmed that Verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Moreover, continuous use of oral Verapamil delayed T1D progression, promoted endogenous beta-cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of Verapamil in T1D.
Verapamil in the treatment of PSVT
Ann Emerg Med 1981 Oct;10(10):538-44.PMID:7025710DOI:10.1016/s0196-0644(81)80013-3.
Verapamil is considered by many investigators to be the drug of choice for the acute management of uncomplicated PSVT. Several clinical investigators have demonstrated termination of PSVT in more than 90% of their patients within minutes following IV drug administration. The incidence of reported severe adverse reactions has been less than 1%. PSVT may be complicated by underlying heart disease, or by antegrade accessory pathway conduction in individuals with pre-excitation syndrome. Such conditions, or the prior use of beta-blocking agents, may contraindicate the use of Verapamil. However, the history of recent myocardial ischemia or the prior use of digitalis does not appear to contraindicate Verapamil therapy. Guidelines for the emergency management of the patient in PSVT are presented.
Verapamil (Isoptin, Knoll; Calan, Searle)
Drug Intell Clin Pharm 1982 Jun;16(6):443-7.PMID:7047130DOI:10.1177/106002808201600601.
Verapamil is a calcium antagonist that is pharmacologically different from other currently marketed antiarrhythmics. It is used for the acute treatment of PSVT and atrial fibrillation and flutter. It appears to be more effective than beta-adrenergic blocking agents in the treatment of PSVT. Approximately 80 percent of patients with PSVT will convert to normal sinus rhythm after Verapamil 0.075-0.15 mg/kg. Atrial fibrillation and flutter seldom convert to sinus rhythm with Verapamil, but it successfully reduces the ventricular rate in 90 percent of these patients. Verapamil is useful for the rapid conversion of PSVT to normal sinus rhythm and for the rapid control of ventricular rate in atrial fibrillation and flutter before other antiarrhythmics have taken effect. Because of its short plasma half-life, other agents or cardioversion can be used if Verapamil is unsuccessful. The use of Verapamil in the treatment of classical and variant angina, hypertrophic cardiomyopathy, and hypertension is being evaluated. Mild reduction in blood pressure and heart rate may occur with Verapamil therapy. Caution must be exercised when Verapamil is administered to patients with sinus node disease, advanced AV block, concomitant beta-adrenergic blocking agents, and digitalis intoxication.