Azimilide Dihydrochloride
(Synonyms: 盐酸阿齐利特,NE-10064 dihydrochloride) 目录号 : GC35453
A class III antiarrhythmic agent
Cas No.:149888-94-8
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
Azimilide is a class III antiarrhythmic agent.1 It blocks rapidly activating delayed rectifier (IKr) and slowly activating delayed rectifier (IKs) potassium currents in isolated guinea pig ventricular myocytes (IC50s = 0.3 and 3 μM, respectively). Azimilide (0.1-10 μM) prolongs action potential duration (APD) in isolated calf Purkinje fibers and ventricular trabeculae in a concentration-dependent manner. It increases the effective refractory period (ERP) in isolated perfused guinea pig hearts and ferret papillary muscles. Azimilide (0.3-30 mg/kg) increases ERP and the absolute refractory period and decreases heart rate in dogs. It reduces mean arrhythmia score in a rat model of coronary artery ligation and reperfusion-induced severe ventricular arrhythmia. Azimilide (10-30 mg/kg) also prevents sustained and non-sustained ventricular tachyarrhythmias in dogs.
1.Salata, J.J., and Brooks, R.R.Pharmacology of azimilide dihydrochloride (NE‐10064), a class III antiarrhythmic agentCardiovasc. Drug Rev.15(2)137-156(2007)
| Cas No. | 149888-94-8 | SDF | |
| 别名 | 盐酸阿齐利特,NE-10064 dihydrochloride | ||
| Canonical SMILES | O=C1N(CCCCN2CCN(C)CC2)C(CN1/N=C/C3=CC=C(C4=CC=C(Cl)C=C4)O3)=O.[H]Cl.[H]Cl | ||
| 分子式 | C23H30Cl3N5O3 | 分子量 | 530.88 |
| 溶解度 | DMSO: 8.46 mg/mL (15.94 mM and warming) | 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 | 1.8837 mL | 9.4183 mL | 18.8366 mL |
| 5 mM | 0.3767 mL | 1.8837 mL | 3.7673 mL |
| 10 mM | 0.1884 mL | 0.9418 mL | 1.8837 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。
Azimilide Dihydrochloride, a novel antiarrhythmic agent
Am J Cardiol 1998 Mar 19;81(6A):40D-46D.PMID:9537222DOI:10.1016/s0002-9149(98)00152-0.
Azimilide, a novel class III antiarrhythmic agent, blocks both the slowly activating (IKs) and rapidly activating (IKr) components of the delayed rectifier potassium current, which distinguishes it from conventional potassium channel blockers such as sotalol and dofetilide, which block only IKr. Azimilide is being developed to prolong the time to recurrence of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia in patients with and without structural heart disease. Azimilide is also being studied for its role in prevention of sudden cardiac death in high-risk patients after myocardial infarction (MI). Preclinical and clinical studies indicate that azimilide prolongs cardiac refractory period in a dose-dependent manner, as manifested by increases in action potential duration, QTc interval, and effective refractory period. Azimilide does not affect PR or QRS interval and minimally affects hemodynamic properties such as blood pressure and heart rate. Its in vivo effects appear to be rate-independent and are maintained under ischemic or hypoxic conditions, properties of potential clinical significance. Azimilide has shown excellent efficacy (>85%) in suppressing supraventricular arrhythmias in a variety of dog models. It also suppressed complex ventricular arrhythmias in infarcted dogs and, in a sudden death cardiac model, decreased mortality. Azimilide pharmacokinetics are very predictable. The drug is completely absorbed, and the extent of absorption is not affected by food. It can be administered once daily. Clinical data suggest that dose adjustments of azimilide are not required for age, gender, hepatic or renal function, or concomitant use of digoxin or warfarin. Azimilide has a good safety profile in open-label safety studies in >800 supraventricular arrhythmia patients, most with structural heart disease. The incidence of serious adverse events, including torsade de pointes, is low. The rate of patient withdrawal from long-term studies is also encouragingly low. Unlike amiodarone, azimilide has shown no evidence of pulmonary or ocular toxicity. Azimilide is expected to provide a unique new therapy for the prevention of supraventricular arrhythmias and sudden cardiac death when Phase III clinical trials are complete and safety and efficacy are confirmed.
Azimilide Dihydrochloride
Expert Rev Cardiovasc Ther 2005 May;3(3):387-91.PMID:15889966DOI:10.1586/14779072.3.3.387.
Azimilide Dihydrochloride is an antiarrhythmic drug with Vaughn Williams class III properties, which blocks both fast (IKr) and slow (IKs) components of the delayed rectifier cardiac potassium channel. The drug slows the heart rate slightly and, like other class III antiarrhythmic drugs, prolongs ventricular repolarization and thus, the QT interval. Unlike sotalol, another class III antiarrhythmic drug, azimilide does not exhibit reverse-use dependence, that is, its binding characteristics and effectiveness are not related to the heart rate. Azimilide is 85% bioavailable, reaches peak blood concentrations in 6-8 h and has a long elimination half-life of 114 h. Clinical trials have utilized once-daily dosing. These trials have tested the use of the drug for patients with supraventricular and ventricular arrhythmias.
Azimilide Dihydrochloride: a new class III anti-arrhythmic agent
Expert Opin Investig Drugs 2000 Nov;9(11):2705-15.PMID:11060832DOI:10.1517/13543784.9.11.2705.
Azimilide Dihydrochloride (Stedicor) is a new class III anti-arrhythmic agent that is being developed by Proctor & Gamble to treat supraventricular and ventricular arrhythmias. Development of this agent is being undertaken due to the high prevalence of atrial fibrillation and the lack of satisfactory therapy for this arrhythmia, along with the desire to develop therapy to reduce the risk of life-threatening ventricular arrhythmias in patients following myocardial infarction. The mechanism of action of azimilide is to block both the slowly conducting (I(Ks)) and rapidly conducting (I(Kr)) rectifier potassium currents in cardiac cells. This differs from other class III agents that block I(Kr) exclusively or in combination with sodium, calcium, or transient outward (I(to)) potassium current channels. Azimilide is distinguished by a relative lack of reverse use-dependence, excellent oral absorption, no need for dose titration, an option for out-patient initiation, no need for adjustment associated with renal or liver failure and a lack of interaction with warfarin or digoxin. It carries some risk of torsade de pointes and rarely, neutropoenia. Azimilide has shown dose-related efficacy in prolonging the time to recurrence of atrial fibrillation. A large trial examining the impact of azimilide on mortality in high-risk patients following myocardial infarction has completed enrolment and should yield data in the next couple of years and further studies are planned. Even if this trial fails to show a survival benefit, a neutral effect on mortality will make the agent attractive for atrial arrhythmias.
Azimilide Dihydrochloride: a unique class III antiarrhythmic agent
Heart Dis 1999 May-Jun;1(2):114-6.PMID:11720612doi
The introduction of class III (Vaughn Williams classification) antiarrhythmic agents has improved the available drug treatment modalities for managing cardiac supraventricular and ventricular tachyarrhythmia. An appreciation of the importance of the delayed rectifier potassium current in the pathogenesis of various cardiac arrhythmias has led to the development of azimilide, an oral type III potassium channel blocker agent that blocks both the rapid activating component (I(kr), common to sotalol, amiodarone, and ibutilide) and the slow activating component (I(ks), a unique action of azimilide) of the delayed rectifier potassium current. Both preclinical and clinical studies have demonstrated the efficacy of azimilide and its safety in the management of supraventricular and ventricular tachyarrhythmia. Azimilide also is being studied in a worldwide multicenter trial for prevention of sudden cardiac death in patients after myocardial infarction. Azimilide soon will become available for clinical use as a treatment for preserving normal sinus rhythm in patients with atrial fibrillation and paroxysmal atrial tachycardia.
Effect of age and gender on azimilide pharmacokinetics after a single oral dose of Azimilide Dihydrochloride
J Clin Pharmacol 1997 Oct;37(10):946-53.PMID:9505986DOI:10.1002/j.1552-4604.1997.tb04269.x.
Azimilide is a new class III antiarrhythmic drug that blocks K+ channels. To determine the effects of age and gender on azimilide pharmacokinetics, a single 150-mg oral dose was administered to 66 healthy volunteers in a 3 x 2 factorial design (age groups of 18-40, 41-64, and > or = 65 years). Blood and urine were analyzed for azimilide and metabolites. The single dose was well-tolerated. Azimilide was 94% plasma protein-bound, and binding was not affected by age or gender. Age does not affect azimilide pharmacokinetics. The renal clearance of azimilide was significantly higher in women than in men (19%), but oral clearance did not differ between genders. Although the maximum azimilide concentration (Cmax) was 27% higher in women, time to maximum concentration or area under the azimilide concentration-time curve were not different from those for men. Body weight-adjusted Cmax did not differ between genders. Dosing adjustments based on either age or gender are not required.