Lidoflazine
(Synonyms: 利多氟嗪) 目录号 : GC38537
Lidoflazine 是 HERG K+ 通道的高亲和力阻滞剂。Lidoflazine 也是一种抗心绞痛的钙通道阻滞剂，具有延长 QT 间期和发生室性心律失常的重大风险。
Cas No.:3416-26-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Lidoflazine is a high affinity blocker of the HERG (human ether-a-go-go-related gene) K+ channel. Lidoflazine is an antianginal calcium channel blocker that carries a significant risk of QT interval prolongation and ventricular arrhythmia[1].
Lidoflazine inhibits potently HERG current (IHERG) recorded from HEK 293 cells stably expressing wild-type HERG (IC50 of ~16 nM).
[1]. https://www.ncbi.nlm.nih.gov/pubmed/15135665
| Cas No. | 3416-26-0 | SDF | |
| 别名 | 利多氟嗪 | ||
| Canonical SMILES | O=C(NC1=C(C)C=CC=C1C)CN2CCN(CCCC(C3=CC=C(F)C=C3)C4=CC=C(F)C=C4)CC2 | ||
| 分子式 | C30H35F2N3O | 分子量 | 491.62 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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 | 2.0341 mL | 10.1705 mL | 20.3409 mL |
| 5 mM | 0.4068 mL | 2.0341 mL | 4.0682 mL |
| 10 mM | 0.2034 mL | 1.017 mL | 2.0341 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 |
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| % 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。
Treatment for calcium channel blocker poisoning: a systematic review
Clin Toxicol (Phila) 2014 Nov;52(9):926-44.PMID:25283255DOI:10.3109/15563650.2014.965827.
Context: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. Objective: To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Methods: Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or Lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. Results: The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. Conclusions: The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.
Lidoflazine in the management of angina pectoris
Clin Cardiol 1979 Dec;2(6):407-12.PMID:397016DOI:10.1002/clc.4960020604.
The effect of Lidoflazine administration (120 mg t.i.d. for 9 weeks) on work tolerance (bicycle ergometer), frequency of anginal attacks, and nitroglycerin consumption was investigated in 28 male patients with stable angina pectoris in a combined single-blind/double-bline study. Lidoflazine increased work tolerance and reduced the frequency of anginal attacks and nitroglycerin consumption. The higher work tolerance level was reached at maximal heart rate and heart rate--systolic blood pressure product values similar to those before treatment. The values of these variables after 3 min of exercise at 60 W, however, were significantly lower after treatment with Lidoflazine. These findings indicate that the heart is performing more economically during Lidoflazine treatment. The improved work tolerance can probably be ascribed to Lidoflazine and not to a training effect because of the significant reduction of this variable in the patients allocated to placebo as compared to those remaining on Lidoflazine treatment. The side effects were generally slight. In one patient the prolongation of the QT interval due to Lidoflazine resulted in rhythm disturbances.
Lidoflazine is a high affinity blocker of the HERG K(+)channel
J Mol Cell Cardiol 2004 May;36(5):701-5.PMID:15135665DOI:10.1016/j.yjmcc.2004.02.009.
Lidoflazine is an antianginal calcium channel blocker that carries a significant risk of QT interval prolongation and ventricular arrhythmia. We investigated whether or not Lidoflazine inhibits current through the rapid delayed rectifier K(+) channel alpha subunit (encoded by HERG - human ether-a-go-go-related gene), since this channel has been widely linked to drug-induced QT-prolongation. Lidoflazine inhibited potently HERG current (I(HERG)) recorded from HEK 293 cells stably expressing wild-type HERG (IC(50) of approximately 16 nM). It was approximately 13-fold more potent against HERG than was verapamil under similar conditions. On membrane depolarization, I(HERG) inhibition developed gradually, ruling out closed-channel state dependent inhibition. The effect of command voltage on the drug's action suggested that Lidoflazine preferentially inhibits activated/open HERG channels. The S6 mutation Y652A largely eliminated the inhibitory action of Lidoflazine, whilst the F656A mutation also reduced blocking potency. We conclude: first, that Lidoflazine produces high affinity blockade of the alpha subunit of the HERG channel by binding to aromatic amino acid residues within the channel pore and, second, that this is likely to represent the molecular mechanism of QT interval prolongation by this drug.
The pathophysiology of angina pectoris and the effect of Lidoflazine
Circulation 1982 Jan;65(1 Pt 2):I27-32.PMID:7030519doi
Angina pectoris results from a deficiency in myocardial oxygen supply. The rate-pressure product is an important predictor of myocardial oxygen requirements in patients with ischemic heart disease and in normal persons. The rate-pressure product at the onset of angina pectoris is reproducible under a variety of circumstances with a suitable protocol. In some patients, coronary artery spasm may reduce myocardial blood flow and contribute to the development of angina pectoris. Lidoflazine is a synthetic drug that appears to be a calcium-entry blocker and results in symptomatic improvement in patients with angina pectoris. Lidoflazine reduces the exercising rate-pressure product by its effect on heart rate and by decreasing systemic vascular resistance. It decreases coronary vascular resistance and antagonizes processes leading to an increase in coronary vasomotor tone.
Beneficial and detrimental effects of Lidoflazine in microvascular angina
Am J Cardiol 1990 Jul 1;66(1):37-41.PMID:2193496DOI:10.1016/0002-9149(90)90732-g.
Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking Lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, Lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/- 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST-segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking Lidoflazine. Repeat invasive study of coronary flow in 11 patients taking Lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred Lidoflazine and all demonstrated improved exercise capacity with Lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking Lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, Lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias.