(S)-Verapamil hydrochloride
(Synonyms: S-维拉帕米,(S)-(-)-Verapamil hydrochloride) 目录号 : GC60008
(S)-Verapamil hydrochloride (S(-)-Verapamil hydrochloride) 通过 MRP1 抑制白三烯 C4 (LTC4) 和钙黄绿素的转运。(S)-Verapamil hydrochloride 导致潜在耐药性肿瘤细胞死亡。
Cas No.:36622-28-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(S)-Verapamil hydrochloride (S(-)-Verapamil hydrochloride) inhibits leukotriene C4 (LTC4) and calcein transport by MRP1. (S)-Verapamil hydrochloride leads to the death of potentially resistant tumor cells[1].
(S)-Verapamil hydrochloride (S(-)-Verapamil hydrochloride) not the (R)-Verapamil hydrochloride potently induces the death of MRP1-transfected BHK-21 cells[1]. (S)-Verapamil hydrochloride is good active form and has the low bioavailability[1].
[1]. Perrotton T, et al. (R)- and (S)-verapamil differentially modulate the multidrug-resistant protein MRP1. J Biol Chem. 2007 Oct 26;282(43):31542-8. Epub 2007 Jul 22. [2]. Tannergren C, et al. St John's wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther. 2004 Apr;75(4):298-309.
| Cas No. | 36622-28-3 | SDF | |
| 别名 | S-维拉帕米,(S)-(-)-Verapamil hydrochloride | ||
| Canonical SMILES | COC1=C(OC)C=CC(CCN(C)CCC[C@@](C#N)(C2=CC(OC)=C(OC)C=C2)C(C)C)=C1.Cl | ||
| 分子式 | C27H39ClN2O4 | 分子量 | 491.06 |
| 溶解度 | 储存条件 | ||
| 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0364 mL | 10.1821 mL | 20.3641 mL |
| 5 mM | 0.4073 mL | 2.0364 mL | 4.0728 mL |
| 10 mM | 0.2036 mL | 1.0182 mL | 2.0364 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Verapamil hydrochloride: pharmacological properties and role in cardiovascular therapeutics
Pharmacotherapy 1982 Nov-Dec;2(6):328-353.PMID:6762530DOI:10.1002/j.1875-9114.1982.tb03210.x.
Verapamil hydrochloride, a prototype calcium antagonist, is now marketed in the United States for the acute treatment of supraventricular tachyarrhythmias and for chronic management of vasospastic and chronic stable angina. It inhibits the slow inward channel in in the heart and blocks calcium influx in smooth muscle. Its intrinsic negative inotropic action, which is apparent in isolated tissues, is offset in vivo by peripheral vasodilation. It has a mild, noncompetitive sympathetic antagonist effect; its most important electrophysiologic action is a depression of AV nodal conduction, accounting for its effect in supraventricular tachyarrhythmias. Its hemodynamic actions are characterized by a complex interplay of changes in preload, afterload, contractility, heart rate, and coronary blood flow. It does not depress cardiac function, except in severe heart failure. The drug has a mild dilator action on coronary arteries and reverses ergonovine-induced vasoconstriction. Controlled trials have established its role in Prinzmetal'S variant angina, unstable angina, and chronic stable angina. It has also been found to be effective in obstructive cardiomyopathies. The potential role of verapamil in such conditions as hypertension, cardioprotection, and Raynaud'S phenomenon needs further evaluation; at present these indications have not been approved by the Food and Drug Administration. The most common side effects include constipation, skin rash, and dizziness; AV block, heart failure, and sinus arrest may occasionally be encountered, especially when ventricular function is compromised or conduction system disease is present.
Tarka® (trandolapril/verapamil hydrochloride extended-release) overdose
J Emerg Med 2011 Mar;40(3):291-5.PMID:19249183DOI:10.1016/j.jemermed.2008.10.015.
Background: Patients with fixed-dose combination product overdoses involving verapamil and trandolapril may present differently than sole calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACE-I) overdose alone, and may have implications for the toxicological management. The ACE-I component may confound the traditional response to antidotal and supportive therapy recommended for CCB overdoses. In such cases, it may be prudent to manage the trandolapril component concurrently while administering traditional CCB antidotes. Objectives: To report a probable case and review the toxicological management of a fixed-dose antihypertensive combination product toxicity involving verapamil and trandolapril (Tarka®). Case report: A 60-year-old man experienced dizziness and fell after ingesting five tablets of Tarka®. Eight hours later, he was found to be hypotensive and bradycardic. Therapy for CCB toxicity was initiated, including fluids, modified hyperglycemia-euglycemia insulin therapy, calcium chloride, activated charcoal, and glucagon. The patient'S blood pressure and heart rate stabilized only after the administration and titration of dopamine and episodes of profuse vomiting in response to glucagon. The patient was transferred to the Cardiac Intensive Care Unit for further monitoring. He was considered stable to the point of all therapies being discontinued only 12 h post-ingestion. The patient was discharged 40 h after ingestion with no further sequelae. Conclusions: Lack of familiarity with the components of fixed-dose combination products poses a problem during overdose situations and may confound the presentation and delay resuscitation and acute stabilization.
Calcium-channel blocking agents
Clin Pharm 1982 Jan-Feb;1(1):17-33.PMID:6764159doi
The role of calcium in the cardiovascular system, and the pharmacology, pharmacokinetics, and studies evaluating the clinical use of three calcium-channel blocking agents--verapamil hydrochloride, nifedipine, and diltiazem hydrochloride--are reviewed. Inhibition of calcium conductance and alteration of calcium availability cause profound changes in: slow inward current of the cardiac action potential, myocardial contractility and metabolism, blood pressure regulation, and smooth-muscle activity. Calcium-channel blocking agents affect the movement of calcium through these channels in smooth and cardiac muscle; the specific agents in this class differ markedly in their inhibitory effects. Verapamil hydrochloride is useful intravenously for treating supraventricular rhythm disturbances. It is absorbed well when taken orally, but there is an extensive first-pass effect, so that about 20% enters the systemic circulation. The incidence of side effects in patients receiving verapamil is 9-10%; about 1% require discontinuation of therapy. Verapamil is contraindicated in patients with sinus-node disease, unstable atrioventricular block, and shock. Nifedipine has proven useful for hypertension, coronary-artery spasm, and exertional angina; it has little negative inotropic effect. Approximately 90% of an oral dose is absorbed, and 65-70% reaches the systemic circulation after first-pass metabolism. Protein binding of nifedipine ranges from 92 to 98%. Side effects of nifedipine, usually associated with the peripheral vasodilatory action, occur in approximately 15% of patients, requiring discontinuance in 2-5%. Diltiazem hydrochloride has been shown effective in the treatment of coronary-artery spasm; limited studies indicate it may be useful in treating exertional angina, hypertension, and possibly arrhythmias. Diltiazem'S oral bioavailability is good (90% reaches systemic circulation), but there is significant interindividual variability between administered dose and resulting plasma concentration. Geriatric patients have delayed absorption and reduced clearance of diltiazem given in sustained-release tablets. Studies of diltiazem are limited at this time. The exact role of calcium-channel blocking agents has not yet been elucidated. However, their ability to influence the calcium channel greatly expands the therapeutic armamentarium for cardiovascular disease and other disorders.
Determination of Verapamil Hydrochloride and Norverapamil Hydrochloride in Rat Plasma by Capillary Electrophoresis With End-Column Electrochemiluminescence Detection and Their Pharmacokinetics Study
J Chromatogr Sci 2021 Feb 15;59(3):289-296.PMID:33333557DOI:10.1093/chromsci/bmaa098.
In this study, we developed a new method for simultaneous determination of verapamil hydrochloride (VerHCl) and its metabolite norverapamil hydrochloride (NorHCl) by using the capillary electrophoresis-electrochemiluminescence. Under optimized experimental conditions, the linear ranges of the VerHCl and NorHCl concentrations were 0.015-10.0 and 0.060-10.0 μg/mL, respectively. The linearity relations were determined using the respective regression equations y = 581.2x + 19.94 and y = 339.4x + 29.16. The respective limits of detection (S/N = 3) were 0.006 and 0.024 μg/mL. The proposed method was used to study the pharmacokinetics of both agents in rat plasma. The maximum concentration (Cmax), half-life time (T1/2) and time to peak (Tmax) were 683.21 ± 74.81 ng/mL, 0.52 ± 0.21 h and 2.49 ± 0.32 h for VerHCl and 698.42 ± 71.45 ng/mL, 1.14 ± 0.26 h and 2.83 ± 0.23 h for NorHCl, respectively, following oral administration of 10 mg/kg VerHCl.
Microneedle-assisted delivery of verapamil hydrochloride and amlodipine besylate
Eur J Pharm Biopharm 2014 Feb;86(2):284-91.PMID:24176676DOI:10.1016/j.ejpb.2013.10.007.
The aim of this project was to study the effect of stainless steel solid microneedles and microneedle rollers on percutaneous penetration of verapamil hydrochloride and amlodipine besylate. Verapamil, 2-(3,4-dimethooxyphenyl)-5-[2-(3,4 dimethoxyphenyl)ethyl-methyl-amino]-2-propan-2-yl-pentanenitrile is a calcium channel blocker agent that regulates high blood pressure by decreasing myocardial contractilty, heart rate and impulse conduction. Amlodipine, (R, S)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1, 4-dihydropyridine, is a calcium channel blocker that is used for the management of hypertension and ischemic heart disease. Passive penetration of verapamil and amlodipine across the skin is low. In vitro studies were performed with microneedle-treated porcine ear skin using vertical static Franz diffusion cells (PermeGear, Hellertown, PA, USA). The receiver chamber contained 5ml of PBS (pH7.4) and was constantly maintained at 37°C temperature with a water circulation jacket. The diffusion area of the skin was 1.77cm(2). The donor compartment was loaded with 1ml of the solution containing 2.5mg/ml of amlodipine besylate. The donor chamber was covered with parafilm to avoid evaporation. Passive diffusion across untreated porcine skin served as control. Aliquots were taken every 2h for 12h and analyzed by liquid chromatography-mass spectrometry. Transcutaneous flux of verapamil increased significantly from 8.75μg/cm(2)/h to 49.96μg/cm(2)/h across microneedle-roller treated porcine skin. Percutaneous flux of amlodipine besylate following the use of stainless steel microneedles was 22.39μg/cm(2)/h. Passive flux for the drug was 1.57μg/cm(2)/h. This enhancement of amlodipine flux was statistically significant. Transdermal flux of amlodipine with microneedle roller was 1.05μg/cm(2)/h in comparison with passive diffusion flux of 0.19μg/cm(2)/h. The difference in flux values was also statistically significant. Stainless steel solid microneedles and microneedle rollers increased percutaneous penetration of verapamil hydrochloride and amlodipine besylate. It may be feasible to develop transdermal microneedle patches for these drugs.