NAV

Encainide

Identification

Summary

Encainide is a voltage-gated sodium channel blocker used for management of atrial or ventricular fibrillation, atrial flutter, and ventricular tachycardia, that is no longer used due to proarrhythmic adverse effects.

Generic Name
Encainide
DrugBank Accession Number
DB01228
Background

All drug products containing encainide hydrochloride. Encainide hydrochloride, formerly marketed as Enkaid capsules, was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack. The manufacturer of Enkaid capsules voluntarily withdrew the product from the US market on December 16, 1991.

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
3D
Similar Structures
Weight
Average: 352.4699
Monoisotopic: 352.21507815
Chemical Formula
C22H28N2O2
Synonyms
  • (±)-2'-[2-(1-methyl-2-piperidyl)ethyl]-p-anisanilide
  • (±)-4-methoxy-N-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)benzamide
  • 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide
  • 4-Methoxy-N-{2-[2-(1-methyl-piperidin-2-yl)-ethyl]-phenyl}-benzamide
  • Encainida
  • Encainide
  • Encainidum
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Pharmacology

Indication

Encainide is a class Ic antiarrhythmic agent which was used for management of irregular heartbeats, such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Used to treat irregular heartbeats, encainide decreases excitability, conduction velocity, and automaticity as a result of slowed atrial, atrioventricular (AV) nodal, His-Purkinje, and intraventricular conduction. It causes a slight but significant prolongation of refractory periods in these tissues. The greatest effect is on the His-Purkinje system. Encainide decreases the rate of rise of the action potential without markedly affecting its duration.

Mechanism of action

Encainide is a sodium channel blocker, binding to voltage gated sodium channels. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hover over products below to view reaction partners

Route of elimination

A radiolabeled dose of encainide is excreted in approximately equal amounts in the urine and feces.

Half-life

1-2 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbataceptThe metabolism of Encainide can be increased when combined with Abatacept.
AbirateroneThe metabolism of Encainide can be decreased when combined with Abiraterone.
AcebutololAcebutolol may increase the arrhythmogenic activities of Encainide.
AcetaminophenThe metabolism of Encainide can be decreased when combined with Acetaminophen.
AcetyldigitoxinAcetyldigitoxin may increase the arrhythmogenic activities of Encainide.
Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Encainide hydrochloride4CH7J36N9S66794-74-9OJIIZIWOLTYOBS-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnkaidCapsule, gelatin coated25 mg/1OralBristol-Myers Squibb Company2009-06-012010-01-31US flag
EnkaidCapsule, gelatin coated35 mg/1OralBristol-Myers Squibb Company2008-01-012008-02-28US flag

Categories

ATC Codes
C01BC08 — Encainide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Alkaloids and derivatives / Benzamides / Anisoles / Phenoxy compounds / Benzoyl derivatives / Methoxybenzenes / Alkyl aryl ethers / Aralkylamines / Piperidines / Trialkylamines
show 6 more
Substituents
Alkaloid or derivatives / Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzamide / Benzanilide
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, benzamides (CHEBI:4788)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
SY3J0147NB
CAS number
66778-36-7
InChI Key
PJWPNDMDCLXCOM-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-methoxy-N-{2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl}benzamide
SMILES
COC1=CC=C(C=C1)C(=O)NC1=CC=CC=C1CCC1CCCCN1C

References

Synthesis Reference
US3931195A
General References
Not Available
Human Metabolome Database
HMDB0015359
KEGG Drug
D07894
KEGG Compound
C06978
PubChem Compound
48041
PubChem Substance
46504470
ChemSpider
43697
RxNav
42368
ChEBI
4788
ChEMBL
CHEMBL315838
Therapeutic Targets Database
DAP000519
PharmGKB
PA449459
Wikipedia
Encainide

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedPreventionCardiac Arrest / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Myocardial Infarction / Myocardial Ischemia / Sudden Cardiac Death / Ventricular Arrhythmia1
2CompletedTreatmentArrhythmia / Cardiovascular Disease (CVD) / Ventricular Arrhythmia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
Dosage Forms
FormRouteStrength
Capsule, gelatin coatedOral25 mg/1
Capsule, gelatin coatedOral35 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00401 mg/mLALOGPS
logP4.29ALOGPS
logP4.49Chemaxon
logS-4.9ALOGPS
pKa (Strongest Acidic)15.52Chemaxon
pKa (Strongest Basic)9.48Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area41.57 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity107.77 m3·mol-1Chemaxon
Polarizability41.04 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.982
Blood Brain Barrier+0.9971
Caco-2 permeable+0.6987
P-glycoprotein substrateSubstrate0.7378
P-glycoprotein inhibitor IInhibitor0.7942
P-glycoprotein inhibitor IIInhibitor0.7384
Renal organic cation transporterInhibitor0.6042
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.801
CYP450 1A2 substrateNon-inhibitor0.6227
CYP450 2C9 inhibitorNon-inhibitor0.8374
CYP450 2D6 inhibitorInhibitor0.802
CYP450 2C19 inhibitorNon-inhibitor0.8697
CYP450 3A4 inhibitorNon-inhibitor0.5837
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6446
Ames testNon AMES toxic0.6098
CarcinogenicityNon-carcinogens0.9485
BiodegradationNot ready biodegradable0.881
Rat acute toxicity2.6801 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.818
hERG inhibition (predictor II)Inhibitor0.8095
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-052n-9311000000-985044a85c7ca1fc4601
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-1a531597650d252b3b37
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0309000000-8e6f9175ce44cf5357d9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052r-1913000000-d4e8c20dd3f3a2968bac
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-106u-6569000000-5140313c11a8cb699afd
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900000000-d82486cc91f536c2e173
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052e-8494000000-d9ab25163ea75309bbfb
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-208.7314361
predicted
DarkChem Lite v0.1.0
[M-H]-176.65631
predicted
DeepCCS 1.0 (2019)
[M+H]+209.1191361
predicted
DarkChem Lite v0.1.0
[M+H]+179.01431
predicted
DeepCCS 1.0 (2019)
[M+Na]+209.0164361
predicted
DarkChem Lite v0.1.0
[M+Na]+185.32433
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Sodium channel protein type 5 subunit alpha
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  2. Starmer CF, Lastra AA, Nesterenko VV, Grant AO: Proarrhythmic response to sodium channel blockade. Theoretical model and numerical experiments. Circulation. 1991 Sep;84(3):1364-77. [Article]
  3. Guo J, Zhan S, Somers J, Westenbroek RE, Catterall WA, Roach DE, Sheldon RS, Lees-Miller JP, Li P, Shimoni Y, Duff HJ: Decrease in density of INa is in the common final pathway to heart block in murine hearts overexpressing calcineurin. Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2669-79. Epub 2006 Jun 2. [Article]
  4. Krishnan SC, Josephson ME: ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol. 1998 Nov;9(11):1167-72. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Details1. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A: Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 2002 Feb;53(2):111-22. doi: 10.1046/j.0306-5251.2001.01548.x. [Article]
  2. Flockhart Table of Drug Interactions [Link]

Drug created at June 13, 2005 13:24 / Updated at June 12, 2020 16:51