| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Cardiac sodium channels (Nav1.5). Ethacizine HCl functions primarily as a potent sodium channel blocker, targeting the fast voltage-gated sodium channels in cardiac myocytes. By binding to these channels, it inhibits the rapid influx of sodium ions (INa), which slows the depolarization rate of the cardiac action potential (Phase 0). This leads to a marked reduction in conduction velocity, particularly in the atria, His-Purkinje system, and ventricles. This mechanism prolongs the effective refractory period and suppresses abnormal pacemaker activity.
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| ln Vitro |
In isolated canine ventricular muscle preparations, Ethacizine HCl (NIK-244) demonstrates longer-lasting Class Ic electrophysiological effects compared to Flecainide. It specifically inhibits the depolarizing current responsible for intraatrial and His-Purkinje-ventricular conduction. At a concentration of 1-300 ug injected directly into sinoatrial node preparations, it exhibits negative chronotropic (slowing heart rate), negative inotropic (reducing contractility), and coronary vasodilator effects, confirming its multi-faceted impact on cardiac hemodynamics and electrophysiology.
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| ln Vivo |
NIK-244 (1-300 ug) injected directly into the SA node, PM preparations demonstrated negative chronotropic, negative inotropic and coronary vasodilation effects [1].
In clinical studies, Ethacizine demonstrates high efficacy in the management of paroxysmal atrial fibrillation (AF). In a cohort study of 28 patients with frequent AF paroxysms, treatment with Ethacizine resulted in a 68% efficacy rate for rhythm control. Comparative clinical trials indicate that Ethacizine and propafenone have comparable effects on myocardial inotropic function, though patients treated with Ethacizine show a numerically lower recurrence rate of AF. It is also effective for the acute relief of atrial flutter and fibrillation via intravenous administration. |
| Enzyme Assay |
A standard patch-clamp electrophysiology assay in isolated cardiac myocytes is used. Whole-cell voltage-clamp is performed to record INa (sodium current). Cells are held at -80 mV and stepped to -30 mV to activate channels. Ethacizine HCl (e.g., 1-30 uM) is perfused onto the cell. The reduction in peak sodium current amplitude is measured to calculate the IC₅0. The voltage-dependence of block and recovery from inactivation are also assessed by varying the pre-pulse potentials.
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| Cell Assay |
Isolated canine cardiac myocytes or Purkinje fibers are used. Cells or tissues are superfused with Tyrode's solution and stimulated at a fixed cycle length (e.g., 1 Hz). Intracellular microelectrodes are used to record action potentials. Ethacizine HCl (1-30 uM) is added to the perfusate. Key parameters measured include the maximum upstroke velocity (Vmax, an indicator of sodium channel conductance), action potential amplitude (APA), and action potential duration (APD). Inhibition of Vmax confirms sodium channel blockade.
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| Animal Protocol |
Canine isolated, blood-perfused heart preparations are used. In a donor dog support system, the sinoatrial (SA) node and papillary muscle (PM) are isolated and cross-circulated with a donor dog. Ethacizine HCl (NIK-244) is injected directly into the SA node artery or the PM preparation at doses of 1-300 ug. Sinoatrial rate, ventricular contractile force (measured via a strain gauge), and coronary blood flow are continuously monitored. Drug effects are recorded and compared to baseline and to standard drugs like Flecainide.
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| ADME/Pharmacokinetics |
Ethacizine is administered orally as tablets or intravenously as a solution. In humans, it has a longer-lasting antiarrhythmic effect than Flecainide. For clinical use, the oral bioavailability is high, allowing for predictable dosing. The compound is metabolized extensively in the liver, primarily by CYP3A4 isoenzymes, into several active metabolites that may contribute to its therapeutic effects. The half-life is long enough to support twice-daily oral dosing. Plasma protein binding is moderate. The molecular formula is C22H28ClN3O3S.
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| Toxicity/Toxicokinetics |
As a Class Ic antiarrhythmic, Ethacizine HCl carries a proarrhythmic risk. In patients with a prior myocardial infarction or structural heart disease (such as left ventricular dysfunction), sodium channel blockers can paradoxically increase the risk of ventricular tachycardia (e.g., CAST-like effects). Adverse effects may include mild anticholinergic symptoms (dry mouth, blurred vision), dizziness, and potential negative inotropic effects (reducing cardiac contractility). It should be used cautiously in patients with severe hepatic impairment.
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| References |
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| Additional Infomation |
Ethacizine HCl (Ethacizin) is a pharmacopoeial reference standard and active pharmaceutical ingredient (API) used primarily in Russia and other former Soviet republics. It has not been approved by major regulatory bodies like the FDA (USA), EMA (Europe), or PMDA (Japan). Its use is restricted to research applications or clinical use in specific countries. It is listed as an impurity standard in European Pharmacopoeia monographs for Mebeverine. It is supplied as a solid powder for research and analytical purposes.
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| Molecular Formula |
C22H27N3O3S.HCL
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| Molecular Weight |
449.99402
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| Exact Mass |
449.154
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| CAS # |
57530-40-2
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| PubChem CID |
3044577
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| Appearance |
White to off-white solid powder
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| Boiling Point |
576.7ºC at 760mmHg
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| Flash Point |
302.6ºC
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| LogP |
5.996
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
30
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| Complexity |
557
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VHNXQKLWIQHSOY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H27N3O3S.ClH/c1-4-24(5-2)14-13-21(26)25-17-9-7-8-10-19(17)29-20-12-11-16(15-18(20)25)23-22(27)28-6-3;/h7-12,15H,4-6,13-14H2,1-3H3,(H,23,27);1H
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| Chemical Name |
ethyl N-[10-[3-(diethylamino)propanoyl]phenothiazin-2-yl]carbamate;hydrochloride
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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, avoid exposure to moisture. |
| 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 : ~100 mg/mL (~222.23 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.56 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 25.0 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: ≥ 2.5 mg/mL (5.56 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 25.0 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: ≥ 2.5 mg/mL (5.56 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 | 2.2223 mL | 11.1114 mL | 22.2227 mL | |
| 5 mM | 0.4445 mL | 2.2223 mL | 4.4445 mL | |
| 10 mM | 0.2222 mL | 1.1111 mL | 2.2223 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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