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Identification
NameEncainide
Accession NumberDB01228  (APRD00613)
TypeSmall Molecule
GroupsApproved, Withdrawn
DescriptionAll 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
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EnkaidNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIISY3J0147NB
CAS number66778-36-7
WeightAverage: 352.4699
Monoisotopic: 352.21507815
Chemical FormulaC22H28N2O2
InChI KeyPJWPNDMDCLXCOM-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
IndicationEncainide 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.
Structured Indications Not Available
PharmacodynamicsUsed 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 actionEncainide 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Sodium channel protein type 5 subunit alphaProteinyes
inhibitor
HumanQ14524 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationA radiolabeled dose of encainide is excreted in approximately equal amounts in the urine and feces.
Half life1-2 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Encainide can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Encainide can be decreased when combined with Amiodarone.Approved, Investigational
ArtemetherThe metabolism of Encainide can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Encainide can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Encainide can be decreased when combined with Betaxolol.Approved
BupropionThe metabolism of Encainide can be decreased when combined with Bupropion.Approved
CelecoxibThe metabolism of Encainide can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Encainide can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Encainide can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Encainide can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Encainide can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Encainide can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Encainide can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Encainide can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Encainide can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Encainide can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Encainide can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Encainide can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Encainide can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Encainide can be decreased when combined with Cocaine.Approved, Illicit
DarifenacinThe metabolism of Encainide can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Encainide can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Encainide can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Encainide can be decreased when combined with Desipramine.Approved
DiphenhydramineThe metabolism of Encainide can be decreased when combined with Diphenhydramine.Approved
DronedaroneThe metabolism of Encainide can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Encainide can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Encainide can be decreased when combined with Eliglustat.Approved
FluoxetineThe metabolism of Encainide can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Encainide can be decreased when combined with Fluvoxamine.Approved, Investigational
HaloperidolThe metabolism of Encainide can be decreased when combined with Haloperidol.Approved
ImipramineThe metabolism of Encainide can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Encainide can be decreased when combined with Indinavir.Approved
IsoniazidThe metabolism of Encainide can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Encainide can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Encainide can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Encainide can be decreased when combined with Lorcaserin.Approved
LumefantrineThe metabolism of Encainide can be decreased when combined with Lumefantrine.Approved
MethadoneThe metabolism of Encainide can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Encainide can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Encainide can be decreased when combined with Metoprolol.Approved, Investigational
MirabegronThe metabolism of Encainide can be decreased when combined with Mirabegron.Approved
NevirapineThe metabolism of Encainide can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Encainide can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Encainide can be decreased when combined with Nilotinib.Approved, Investigational
PanobinostatThe serum concentration of Encainide can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Encainide can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Encainide can be decreased when it is combined with Peginterferon alfa-2b.Approved
PromazineThe metabolism of Encainide can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe metabolism of Encainide can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Encainide can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Encainide can be decreased when combined with Ranolazine.Approved, Investigational
RitonavirThe metabolism of Encainide can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Encainide can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Encainide can be decreased when combined with Ropinirole.Approved, Investigational
SertralineThe metabolism of Encainide can be decreased when combined with Sertraline.Approved
StiripentolThe metabolism of Encainide can be decreased when combined with Stiripentol.Approved
TerbinafineThe metabolism of Encainide can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe metabolism of Encainide can be decreased when combined with Thioridazine.Approved
TiclopidineThe metabolism of Encainide can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Encainide can be decreased when combined with Tipranavir.Approved, Investigational
TranylcypromineThe metabolism of Encainide can be decreased when combined with Tranylcypromine.Approved
VenlafaxineThe metabolism of Encainide can be decreased when combined with Venlafaxine.Approved
ZiprasidoneThe metabolism of Encainide can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis Reference

DrugSyn.org

US3931195A
General ReferencesNot Available
External Links
ATC CodesC01BC08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-phenylbenzamides. These are benzamides that are N-linked to a phenyl group via the carboxamide group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-phenylbenzamides
Alternative Parents
Substituents
  • N-phenylbenzamide
  • Alkaloid or derivatives
  • N-arylamide
  • Benzoic acid or derivatives
  • Coniine
  • Methoxybenzene
  • Phenol ether
  • Benzoyl
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

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 protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23