| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Cardiac Sodium Channel NaV1.5 (class 1C antiarrhythmic)
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
Flecainide-d4 (acetate) is the deuterium-labeled analog of flecainide acetate. Flecainide acetate (R-818) is a class 1C antiarrhythmic agent used for the management of supraventricular arrhythmias. It works by blocking the cardiac sodium channel NaV1.5, slowing the upstroke of the action potential and prolonging conduction in the atria, ventricles, and Purkinje fibers. The labeled form is used as a standard. |
| ln Vivo |
No specific in vivo data for the labeled compound. Unlabeled flecainide acetate is a well-established antiarrhythmic drug. It is FDA-approved for the treatment of paroxysmal atrial fibrillation (PAF), paroxysmal supraventricular tachycardia (PSVT), and ventricular tachycardia (VT). It is also used for the management of atrial flutter. Flecainide is classified as a Class 1C antiarrhythmic (membrane stabilizing agent).
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| Enzyme Assay |
Recombinant human cardiac sodium channel NaV1.5 (SCN5A) is expressed in HEK293 cells. Whole-cell patch-clamp recordings are performed. Cells are held at a resting potential (-120 mV) and stepped to a test potential (-10 mV) to measure peak sodium current. Flecainide (0.1-100 uM) is applied, and the inhibition of sodium current is measured. Flecainide exhibits use-dependent block (greater block at higher frequencies of stimulation). IC50 values (e.g., ~1-5 uM for resting block, lower for inactivated state) are determined.
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| Cell Assay |
HEK293 cells expressing human NaV1.5 channels are cultured in DMEM with 10% FBS. Whole-cell patch-clamp electrophysiology is performed at room temperature. The external solution contains NaCl, KCl, CaCl2, MgCl2, HEPES, and glucose. The internal solution contains CsF, CsCl, and EGTA to eliminate potassium currents. Cells are held at -120 mV and stepped to -10 mV. Flecainide (0.1-100 uM) is applied, and the reduction in peak sodium current is measured. For use-dependent block, trains of depolarizing pulses (e.g., 10-100 pulses at 2-10 Hz) are applied.
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| Animal Protocol |
Flecainide-d4 acetate is not administered in vivo as a therapeutic agent; it is an analytical internal standard. Unlabeled flecainide is used in vivo: in animal models, flecainide (1-10 mg/kg, i.v. or p.o.) suppresses ventricular arrhythmias induced by coronary artery ligation in dogs and rats. It also prolongs effective refractory period (ERP) in isolated rabbit heart preparations. These studies supported the drug's clinical development.
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| ADME/Pharmacokinetics |
Flecainide-d4 acetate is not administered in vivo. The unlabeled flecainide is well absorbed orally (90-95% bioavailability). Peak plasma concentrations are reached in 2-4 hours. It is highly plasma protein bound (~40%). The half-life is 12-27 hours (normal metabolizers), allowing twice-daily dosing. It is metabolized in the liver by CYP2D6 to two major metabolites (m-O-dealkylated flecainide and lactam). About 30% is excreted unchanged in urine.
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| Toxicity/Toxicokinetics |
Flecainide-d4 acetate is for research use only. Unlabeled flecainide has known toxicities: common side effects include dizziness, visual disturbances (blurred vision, diplopia), headache, nausea, and fatigue. It has a narrow therapeutic index and can cause proarrhythmia, including ventricular tachycardia/fibrillation (especially in patients with structural heart disease or reduced LVEF). Flecainide also has negative inotropic effects (can worsen heart failure). Class 1C antiarrhythmics are contraindicated after myocardial infarction due to increased mortality (CAST trial).
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| References |
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| Additional Infomation |
Flecainide-d4 acetate (CAS: 1276197-21-7) is a stable isotope-labeled compound used as an internal standard for the quantification of flecainide in biological samples (plasma, urine) for therapeutic drug monitoring (TDM) and pharmacokinetic studies. The deuterium atoms are located on the two 2,2,2-trifluoroethoxy groups (bis(2,2,2-trifluoroethoxy-1,1-d2)). Molecular formula: C19H20D4F6N2O5, molecular weight: 478.42. Synonyms: R-818-d4. For research use only. References: Deuterated standards.
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| Molecular Formula |
C19H24F6N2O5
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|---|---|
| Molecular Weight |
474.394686698914
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| Exact Mass |
478.184
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| CAS # |
1276197-21-7
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| Related CAS # |
Flecainide acetate;54143-56-5
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| PubChem CID |
76973110
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
32
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| Complexity |
531
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(=O)(O)C.C(C1C=C(OC([H])([H])C(F)(F)F)C=CC=1OC([H])([H])C(F)(F)F)(=O)NCC1NCCCC1
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| InChi Key |
RKXNZRPQSOPPRN-PQDNHERISA-N
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| InChi Code |
InChI=1S/C17H20F6N2O3.C2H4O2/c18-16(19,20)9-27-12-4-5-14(28-10-17(21,22)23)13(7-12)15(26)25-8-11-3-1-2-6-24-11;1-2(3)4/h4-5,7,11,24H,1-3,6,8-10H2,(H,25,26);1H3,(H,3,4)/i9D2,10D2;
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| Chemical Name |
acetic acid;2,5-bis(1,1-dideuterio-2,2,2-trifluoroethoxy)-N-(piperidin-2-ylmethyl)benzamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1080 mL | 10.5399 mL | 21.0797 mL | |
| 5 mM | 0.4216 mL | 2.1080 mL | 4.2159 mL | |
| 10 mM | 0.2108 mL | 1.0540 mL | 2.1080 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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