DrugBank: Encainide (DB01228)

targets (1) enzymes (1)

Identification

Name

Encainide

Accession Number

DB01228 (APRD00613)

Type

small molecule

Groups

approved, withdrawn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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Encainida [Spanish]
Encainide [French]
Encainidum [Latin]

Synonyms

Encainida [Spanish]
Encainide [French]
Encainidum [Latin]

Salts

Not Available

Brand names

Name	Company
Enkaid

Brand mixtures

Not Available

Categories

Sodium channel blockers
Antiarrhythmic Agents
Anti-Arrhythmia Agents

CAS number

66778-36-7

Weight

Average: 352.4699
Monoisotopic: 352.21507815

Chemical Formula

C₂₂H₂₈N₂O₂

InChI Key

InChIKey=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)

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

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

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Bristol-Myers Squibb Co.

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
logP	4	PhysProp

Predicted Properties

Property	Value	Source
water solubility	4.01e-03 g/l	ALOGPS
logP	4.29	ALOGPS
logP	4.49	ChemAxon Molconvert
logS	-4.9	ALOGPS
pKa	0	ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	41.57	ChemAxon Molconvert
rotatable bond count	6	ChemAxon Molconvert
refractivity	107.77	ChemAxon Molconvert
polarizability	41.04	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C06978
ChEBI	4788
ChEMBL	4788
Therapeutic Targets Database	DAP000519
Wikipedia	http://en.wikipedia.org/wiki/Encainide

ATC Codes

C01BC08

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Cisapride	Increased risk of cardiotoxicity and arrhythmias

Food Interactions

Not Available

Targets
1. Sodium channel protein type 5 subunit alpha Pharmacological action: yes Actions: inhibitor 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 responsible for the initial upstroke of the action potential in the electrocardiogram Organism class: human UniProt ID: Q14524 Gene: SCN5A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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 responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out

Gene: SCN5A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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
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
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes
1. Cytochrome P450 2D6 Actions: substrate 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 UniProt ID: P10635 Gene: CYP2D6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010. 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. Epub 2009 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 2D6

Actions: substrate

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

UniProt ID: P10635 Link_out

Gene: CYP2D6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
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. Epub 2009 Nov 24. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2012 13:17