Identification

Name
Encainide
Accession Number
DB01228  (APRD00613)
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

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.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Encainide hydrochloride4CH7J36N9S66794-74-9OJIIZIWOLTYOBS-UHFFFAOYSA-N
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EnkaidEncainide hydrochloride (25 mg/1)Capsule, gelatin coatedOralBristol Myers Squibb2006-04-07Not applicableUs
EnkaidEncainide hydrochloride (35 mg/1)Capsule, gelatin coatedOralBristol Myers Squibb2006-04-07Not applicableUs
International/Other Brands
Enkaid
Categories
UNII
SY3J0147NB
CAS number
66778-36-7
Weight
Average: 352.4699
Monoisotopic: 352.21507815
Chemical Formula
C22H28N2O2
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

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.

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
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbirateroneThe serum concentration of Encainide can be increased when it is combined with Abiraterone.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Encainide.
AmitriptylineThe risk or severity of QTc prolongation can be increased when Encainide is combined with Amitriptyline.
AnagrelideThe risk or severity of QTc prolongation can be increased when Encainide is combined with Anagrelide.
ArtemetherThe metabolism of Encainide can be decreased when combined with Artemether.
AtomoxetineThe risk or severity of QTc prolongation can be increased when Atomoxetine is combined with Encainide.
AzithromycinThe risk or severity of QTc prolongation can be increased when Encainide is combined with Azithromycin.
BetaxololThe risk or severity of QTc prolongation can be increased when Encainide is combined with Betaxolol.
BortezomibThe risk or severity of QTc prolongation can be increased when Bortezomib is combined with Encainide.
CelecoxibThe metabolism of Encainide can be decreased when combined with Celecoxib.
Food Interactions
Not Available

References

Synthesis Reference
US3931195A
General References
Not Available
External Links
Human Metabolome Database
HMDB0015359
KEGG Drug
D07894
KEGG Compound
C06978
PubChem Compound
48041
PubChem Substance
46504470
ChemSpider
43697
ChEBI
4788
ChEMBL
CHEMBL315838
Therapeutic Targets Database
DAP000519
PharmGKB
PA449459
Wikipedia
Encainide
ATC Codes
C01BC08 — Encainide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Ventricular Arrythmias1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Death, Sudden,Cardiac / Heart Arrest / Heart Diseases / Myocardial Infarction / Myocardial Ischemia / Ventricular Arrythmias1

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)12.37ChemAxon
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Benzanilide / Benzamide / Benzoic acid or derivatives / Alkaloid or derivatives / Anisole / Phenoxy compound / Benzoyl / Phenol ether / Methoxybenzene / Aralkylamine
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, benzamides (CHEBI:4788)

Targets

Kind
Protein
Organism
Human
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. [PubMed:17016423]
  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. [PubMed:1653123]
  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. [PubMed:16751287]
  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. [PubMed:9835260]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:33