| Size | Price | |
|---|---|---|
| 100mg | ||
| Other Sizes |
| Targets |
Nifekalant targets the IKr potassium channel, which is responsible for the rapid component of the delayed rectifier potassium current in cardiac myocytes. By inhibiting IKr, nifekalant prolongs the action potential duration and the effective refractory period in cardiac tissue. This prolongation of repolarization is the basis for its antiarrhythmic activity. Nifekalant's selectivity for IKr over other ion channels (calcium channels, sodium channels, beta-receptors) distinguishes it from other antiarrhythmic agents. The lack of negative inotropic effect is a significant advantage, as it allows nifekalant to be used in patients with compromised cardiac function.
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| ln Vitro |
Nifekalant has a Ki value of 27 mM for cardiac M2 receptor interaction and 74 mM for peripheral M3 receptor interaction. With an IC50 value of 7.9 mM, nifekalant dose-dependently inhibits HERG channels, however in the Xenopus oocyte expression system, it has no effect on minK currents. In a frequency-dependent way, nifekalant mostly inhibits HERG channels while they are open. Pure K+ channel blockers like Nifekalant do not influence cardiac conduction and do not have the detrimental inotropic effects of amiodarone due to their β-blocking action[2].
In vitro, nifekalant inhibits the IKr potassium channel with an IC50 of 10 µM. The compound's effect on action potential duration is assessed using patch-clamp electrophysiology on isolated cardiac myocytes or heterologous expression systems. Nifekalant prolongs the action potential duration in a concentration-dependent manner. The compound shows no significant activity against calcium channels or beta-receptors, confirming its selectivity for potassium channels. Nifekalant's pure potassium channel-blocking activity distinguishes it from other Class III antiarrhythmic agents such as amiodarone, which has multiple mechanisms of action. |
| ln Vivo |
Before coronary ligation, 3 mg/kg and 10 mg/kg MS-551 raised mean arterial pressure (MAP) by 14% and 33% and lowered heart rate by 6% and 12% in rats (a species lacking in functional cardiac IK). After reperfusion, MS-551 reduces the incidence of prolonged ventricular fibrillation (VF) and lengthens the QT interval[3].
In vivo, nifekalant is used for the acute management of life-threatening ventricular tachyarrhythmias, including ventricular tachycardia and ventricular fibrillation. The compound is administered intravenously in hospital settings, typically in intensive care or emergency departments. Nifekalant effectively terminates ventricular arrhythmias by prolonging the action potential duration and refractory period. The compound's lack of negative inotropic effect makes it particularly useful in patients with heart failure or reduced left ventricular function. Nifekalant has been shown to be effective in patients with refractory ventricular tachyarrhythmias who have failed other antiarrhythmic therapies. |
| Enzyme Assay |
Nifekalant's inhibition of the IKr potassium channel is assessed using electrophysiological techniques. Patch-clamp recordings from heterologous expression systems (e.g., HEK293 cells expressing the hERG channel) or isolated cardiac myocytes are used to measure the effects of nifekalant on IKr currents. Voltage-clamp protocols are employed to assess the concentration-dependent inhibition of IKr. These assays provide quantitative information on the potency and mechanism of nifekalant as an IKr blocker.
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| Cell Assay |
Nifekalant is tested on cultured cardiac myocytes or heterologous expression systems expressing the hERG potassium channel. Cells are treated with varying concentrations of nifekalant; IKr currents are measured using patch-clamp electrophysiology; action potential duration is assessed using current-clamp recordings. These cell-based assays demonstrate the potency and selectivity of nifekalant as an IKr blocker.
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| Animal Protocol |
Nifekalant has been evaluated in animal models of ventricular arrhythmias and in clinical studies. In animal models, nifekalant effectively terminates ventricular tachycardia and fibrillation induced by various interventions. The compound has been studied in clinical trials for the treatment of ventricular tachyarrhythmias, demonstrating efficacy in terminating arrhythmias and improving hemodynamic stability. Nifekalant is approved for clinical use in several countries for the acute management of life-threatening ventricular arrhythmias.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of nifekalant have been conducted in preclinical species and humans. The compound is administered intravenously, with rapid onset of action. Nifekalant has a half-life appropriate for acute management of arrhythmias. The compound is metabolized in the liver and excreted in urine. Pharmacokinetic parameters such as half-life, volume of distribution, and clearance have been characterized in clinical studies. Dose adjustments may be necessary in patients with renal or hepatic impairment.
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| Toxicity/Toxicokinetics |
The primary toxicity associated with nifekalant is proarrhythmia, specifically torsade de pointes, which is a risk associated with all IKr blockers that prolong the QT interval. The risk of torsade de pointes is dose-dependent and is increased in patients with electrolyte abnormalities, bradycardia, or concomitant use of other QT-prolonging drugs. Nifekalant should be administered with continuous ECG monitoring to detect QT prolongation and arrhythmias. Other adverse effects include hypotension and infusion site reactions. The benefit-risk profile of nifekalant is favorable in patients with life-threatening ventricular arrhythmias refractory to other therapies.
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| References |
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| Additional Infomation |
Nifekalan hydrochloride is an amine compound. It contains nifekalan.
See also: Nifekalan (note moved to). Nifekalant hydrochloride (MS-551) is a Class III antiarrhythmic agent that selectively inhibits the IKr potassium channel with an IC50 of 10 µM. Unlike other Class III agents, nifekalant does not block calcium channels or beta-receptors and has no negative inotropic effect. The compound is used for the acute management of life-threatening ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) that are refractory to other therapies. Nifekalant is administered intravenously in hospital settings with continuous ECG monitoring. The compound's selectivity and lack of negative inotropic effect make it a valuable option for patients with compromised cardiac function. Nifekalant is approved for clinical use in several countries. |
| Molecular Formula |
C19H28CLN5O5
|
|---|---|
| Molecular Weight |
441.913
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| Exact Mass |
441.178
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| CAS # |
130656-51-8
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| PubChem CID |
122188
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| Appearance |
White to yellow solid powder
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| Boiling Point |
597.9ºC at 760mmHg
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| Flash Point |
315.4ºC
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| LogP |
1.729
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
30
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| Complexity |
613
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| Defined Atom Stereocenter Count |
0
|
| InChi Key |
YPVGGQKNWAKOPX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H27N5O5.ClH/c1-21-17(14-18(26)22(2)19(21)27)20-9-11-23(12-13-25)10-3-4-15-5-7-16(8-6-15)24(28)29/h5-8,14,20,25H,3-4,9-13H2,1-2H31H
|
| Chemical Name |
2,4(1H,3H)-Pyrimidinedione, 6-((2-((2-hydroxyethyl)(3-(4-nitrophenyl)propyl)amino)ethyl)amino)-1,3-dimethyl-, monohydrochloride
|
| Synonyms |
MS551 MS-551 MS 551
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~282.86 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2629 mL | 11.3145 mL | 22.6290 mL | |
| 5 mM | 0.4526 mL | 2.2629 mL | 4.5258 mL | |
| 10 mM | 0.2263 mL | 1.1315 mL | 2.2629 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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