Encainide targets voltage-gated sodium channels, particularly in cardiac tissue. These channels are responsible for the rapid depolarization phase of the cardiac action potential. By binding to these channels and inhibiting sodium influx, Encainide reduces the rate of depolarization, which slows conduction velocity and prolongs the refractory period. This mechanism is characteristic of class Ic antiarrhythmic agents. The inhibition of sodium channels by Encainide stabilizes the neuronal membrane and suppresses abnormal electrical activity in the heart, which can help to restore normal sinus rhythm. However, the proarrhythmic effects of Encainide, particularly its association with increased mortality in patients with asymptomatic ventricular arrhythmias after a myocardial infarction, led to its withdrawal from the market. The compound's effects on potassium channels in smooth muscle cells have also been investigated, suggesting potential applications beyond cardiac arrhythmias. Encainide is used as a research tool to study sodium channel function and the mechanisms of arrhythmias.

Encainide exhibits in vitro activity as a sodium channel blocker. In patch-clamp electrophysiology studies, Encainide inhibits sodium channel currents in a concentration-dependent manner. This inhibition reduces the rate of depolarization and slows conduction velocity. The compound's effects are characteristic of class Ic antiarrhythmic agents. In addition to its effects on sodium channels, Encainide has been shown to have effects on potassium channels in smooth muscle cells, which may contribute to its overall pharmacological profile. These in vitro findings provide a mechanistic basis for Encainide's antiarrhythmic activity.

His-Purkinje conduction time (HV interval) and intraventricular conduction time (QRS duration) are extended by encainide (0.3, 0.9, 2.7 mg/kg; single-dose infusion); however, it has no effect on the recovery time of the sinoatrial node. Or the conduction of the atrioventricular node is unaffected. or ventricular myocardium, atrioventricular node, or refractory or QT interval of the atrium [1].

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Encainide was used clinically for the management of severe or life-threatening ventricular arrhythmias, including ventricular tachycardia and fibrillation. It was effective in suppressing these arrhythmias in many patients. However, the Cardiac Arrhythmia Suppression Trial (CAST) found that Encainide was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack. This led to its withdrawal from the market. The compound's in vivo effects on cardiac electrophysiology have been studied extensively. It slows conduction velocity and prolongs the refractory period in cardiac tissue, which can help to terminate reentrant arrhythmias. However, its proarrhythmic effects, particularly in patients with ischemic heart disease, limit its clinical utility.

The in vitro enzyme/receptor binding (non-cellular) assay for Encainide is not a typical enzyme inhibition assay, as its primary mechanism involves the blockade of ion channels rather than enzyme inhibition. However, its activity can be studied using electrophysiological techniques. In a typical protocol, voltage-gated sodium channels are expressed in Xenopus oocytes or mammalian cells, and the effects of Encainide on sodium currents are measured using the patch-clamp technique. The compound's ability to inhibit sodium currents is assessed by measuring the reduction in current amplitude and the shift in voltage dependence of activation and inactivation. These assays are crucial for characterizing the compound's mechanism of action at the ion channel level.

The in vitro cellular assay for Encainide typically involves evaluating its effects on cardiac myocytes or other cells expressing voltage-gated sodium channels. In a typical assay, cells are cultured and the effects of Encainide on action potential parameters are measured using microelectrode or patch-clamp techniques. The compound reduces the rate of depolarization (Vmax), slows conduction velocity, and prolongs the refractory period. These effects are consistent with its mechanism as a sodium channel blocker. The compound's effects on potassium channels in smooth muscle cells can also be studied in cellular assays. These cellular assays provide functional evidence for Encainide's activity in a relevant biological context.

The in vivo animal experimental protocol for Encainide typically involves the use of animal models of cardiac arrhythmias. In a typical study, Encainide is administered to dogs or other animals, and its effects on cardiac electrophysiology are measured using electrocardiography (ECG) and intracardiac electrophysiology studies. The compound's ability to suppress induced arrhythmias, such as ventricular tachycardia, is assessed. Additionally, its effects on heart rate, blood pressure, and conduction intervals (PR, QRS, QT) are measured. These in vivo models are essential for demonstrating the compound's antiarrhythmic activity and for understanding its mechanism of action in a whole-organism context.

Absorption, Distribution and Excretion
Radiolabeled encarnib doses are primarily excreted via urine and feces, with roughly equal amounts excreted. Metabolisms/Metabolites Known metabolites of encarnib include O-desmethylencarnib and N-desmethylencarnib. Biological Half-Life 1–2 hours

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Specific pharmacokinetic (PK) data for Encainide are not detailed in the provided references. However, as a drug that was used clinically, its PK properties are well-characterized. Encainide is well-absorbed after oral administration and undergoes extensive hepatic metabolism. It has a half-life of approximately 2-4 hours. The compound is metabolized to active metabolites, which contribute to its antiarrhythmic effects. Further details on its PK properties can be found in the clinical literature.

Encainide was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack, leading to its withdrawal from the market. This proarrhythmic effect is a significant toxicity that limits its clinical use. The mechanism of this toxicity is not fully understood but may involve the slowing of conduction velocity, which can promote reentrant arrhythmias in susceptible patients. Comprehensive toxicological assessments have been conducted during its clinical development.

[1]. R N Brogden, et al. Encainide. A review of its pharmacological properties and therapeutic efficacy. Drugs. 1987 Nov;34(5):519-38.

Encainide is a 4-methoxy-N-phenylbenzamide in which the hydrogen at the 2-position of the benzene ring is replaced by a 2-(1-methylpiperidin-2-yl)ethyl group. As a class Ic antiarrhythmic drug, its hydrochloride salt was used to treat serious or life-threatening ventricular arrhythmias, but was withdrawn from the market due to its association with increased mortality in patients with asymptomatic arrhythmias following recent myocardial infarction. It has both antiarrhythmic and sodium channel blocker effects. It belongs to the piperidine and benzamide classes. All pharmaceutical products containing encainide hydrochloride. Encainide hydrochloride (formerly marketed as Enkaid capsules) was associated with increased mortality in patients with asymptomatic arrhythmias following recent myocardial infarction. The manufacturer of encainide capsules voluntarily withdrew the product from the U.S. market on December 16, 1991. Encainide is an antiarrhythmic drug that slows conduction in the His-Purkinje system and myocardium by blocking voltage-gated sodium channels. Drug Indications Encani is a class Ic antiarrhythmic drug used to treat arrhythmias such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. Mechanism of Action Encani is a sodium channel blocker that binds to voltage-gated sodium channels, stabilizing neuronal membranes by inhibiting the ion flow required for impulse initiation and conduction. It reduces diastolic ventricular excitability and increases the ventricular stimulation threshold. Pharmacodynamics Encani is used to treat arrhythmias by slowing conduction in the atria, atrioventricular node, His-Purkinje system, and within the ventricles, thereby reducing ventricular excitability, conduction velocity, and automaticity. It can slightly but significantly prolong the effective refractory period of these tissues. Its effect on the His-Purkinje system is greatest. Encani reduces the rate of action potential rise but has little effect on its duration.

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Encainide is a class Ic antiarrhythmic agent that was used for the management of severe or life-threatening ventricular arrhythmias. It is a sodium channel blocker. Encainide was withdrawn from the market due to increased death rates in patients with asymptomatic heart rhythm abnormalities after a recent heart attack. The compound has a molecular formula of C22H28N2O2 and a molecular weight of 352.47. It is used in research to study sodium channel function and cardiac electrophysiology.

C22H28N2O2

352.478

352.215

66778-36-7

Encainide hydrochloride;66794-74-9

48041

White to off-white solid powder

4.375

1

3

6

26

434

0

CN1CCCCC1CCC2=CC=CC=C2NC(=O)C3=CC=C(C=C3)OC

PJWPNDMDCLXCOM-UHFFFAOYSA-N

InChI=1S/C22H28N2O2/c1-24-16-6-5-8-19(24)13-10-17-7-3-4-9-21(17)23-22(25)18-11-14-20(26-2)15-12-18/h3-4,7,9,11-12,14-15,19H,5-6,8,10,13,16H2,1-2H3,(H,23,25)

4-methoxy-N-[2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl]benzamide

MJ 9067; Encainide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)