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encainide

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Description

Encainide is an antiarrhythmic drug that was once used to treat ventricular tachycardia and atrial fibrillation. It was withdrawn from the market due to its association with increased mortality. Encainide is a class I antiarrhythmic drug, meaning it acts by blocking sodium channels in the heart. Encainide was synthesized in the 1970s and its effects on cardiac rhythm were studied extensively. The drug was effective in suppressing arrhythmias but was found to increase the risk of sudden cardiac death in some patients, leading to its withdrawal.'

Encainide: One of the ANTI-ARRHYTHMIA AGENTS, it blocks VOLTAGE-GATED SODIUM CHANNELS and slows conduction within the His-Purkinje system and MYOCARDIUM. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

encainide : 4-Methoxy-N-phenylbenzamide in which the hydrogen at the 2 position of the phenyl group is substituted by a 2-(1-methylpiperidin-2-yl)ethyl group. A class Ic antiarrhythmic, the hydrochloride was used for the treatment of severe or life-threatening ventricular arrhythmias, but it was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack and was withdrawn from the market. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID48041
CHEMBL ID315838
CHEBI ID4788
SCHEMBL ID94346
MeSH IDM0025437

Synonyms (50)

Synonym
37612-13-8
4-methoxy-n-{2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl}benzamide
benzamide, 4-methoxy-n-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)-, (+-)-
c22h28n2o2
encainidum [latin]
encainida [spanish]
brn 0497572
mj 9067
encainide [french]
(+-)-4-methoxy-n-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)benzamide
encainide [inn:ban]
C06978
66778-36-7
encainide
(+/-)-4-methoxy-n-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)benzamide
DB01228
4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide
(+/-)-2'-[2-(1-methyl-2-piperidyl)ethyl]-p-anisanilide
4-methoxy-n-{2-[2-(1-methyl-piperidin-2-yl)-ethyl]-phenyl}-benzamide
CHEBI:4788 ,
encainidum
(+-)-2'-[2-(1-methyl-2-piperidyl)ethyl]-p-anisanilide
encainida
4-methoxy-n-[2-[2-(1-methylpiperidin-2-yl)ethyl]phenyl]benzamide
encainide (inn)
D07894
benzamide, 4-methoxy-n-[2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl]-
AKOS016014083
5-22-09-00511 (beilstein handbook reference)
unii-sy3j0147nb
sy3j0147nb ,
encainide [vandf]
encainide [mi]
encainide [who-dd]
encainide [inn]
(+/-)-2'-(2-(1-methyl-2-piperidyl)ethyl)-p-anisanilide
benzamide, 4-methoxy-n-(2-(2-(1-methyl-2-piperidinyl)ethyl)phenyl)-
SCHEMBL94346
CHEMBL315838
4-methoxy-n-(2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl)benzamide #
(.+/-.)-4-methoxy-n-[2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl]benzamide
4-methoxy-n-(2-(2-(1-methylpiperidin-2-yl)ethyl)phenyl)benzamide
benzamide,4-methoxy-n-[2-[2-(1-methyl-2-piperidinyl)ethyl]phenyl]-
DTXSID0022983
Q514534
FT-0720729
NCGC00185765-02
HY-130335
EN300-19765972
CS-0107353

Research Excerpts

Overview

Encainide is a potent Class I antiarrhythmic drug that prolongs conduction in the His-Purkinje system. Encainide proved to be a very useful agent to control incessant supraventricular tachycardia resistant to other antiarr hythmic agents.

ExcerptReferenceRelevance
"Encainide is a new antiarrhythmic agent which is currently undergoing clinical evaluation. "( Myocardial uptake of encainide and its two major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, in the dog.
Gillis, AM; Kates, RE; Latini, R,
)
1.89
"Encainide is an antiarrhythmic agent under evaluation; it is effective in ventricular and supraventricular arrhythmias. "( [Electrophysiological effects of encainide in man].
Bounhoure, JP; Calazel, J; Cassagneau, B; Marin, T; Massabuau, P; Miquel, JP; Narula, OS; Puel, J, 1984
)
1.99
"Encainide is a class Ic antiarrhythmic drug."( Clinical pharmacokinetics of the newer antiarrhythmic agents.
Gillis, AM; Kates, RE,
)
0.85
"Encainide proved to be a very useful agent to control incessant supraventricular tachycardia resistant to other antiarrhythmic agents."( Suppression of incessant supraventricular tachycardia by intravenous and oral encainide.
Abdollah, H; Brugada, P; Wellens, HJ, 1984
)
1.22
"Encainide is a potent Class I antiarrhythmic drug that prolongs conduction in the His-Purkinje system. "( Encainide: a new and potent antiarrhythmic agent.
Harrison, DC; Mason, J; Sami, M; Winkle, R, 1980
)
3.15
"Encainide is a new agent for treating ventricular arrhythmias. "( Antiarrhythmic efficacy of encainide in patients with refractory recurrent ventricular tachycardia.
Mason, JW; Peters, FA, 1981
)
2
"Encainide is an agent effective in atrioventricular and atrioventricular nodal reentrant tachycardia. "( Intravenous 3-methoxy-O-desmethyl-encainide in reentrant supraventricular tachycardia: a randomized double-blind placebo-controlled trial in patients undergoing EP study.
Echt, DS; Hanyok, JJ; Lee, JT; Murray, KT; Roden, DM; Ware, DL, 1991
)
2
"Encainide is a class 1C antiarrhythmic agent that is indicated for the treatment of life-threatening arrhythmias, such as sustained ventricular tachycardia. "( Effect of encainide, ODE, MODE, and flecainide on ADP/5-HT induced platelet aggregation and in the anesthetized dog coronary artery stenosis-occlusion model of intravascular thrombosis.
Antonaccio, MJ; Buchanan, JO; Fleming, JS; Iben, LG; Yocca, FD, 1991
)
2.13
"Encainide (E) is a class I antiarrhythmic agent which is metabolised in humans, with the formation in the majority of patients of O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE). "( The effects of encainide and its major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, on experimental cardiac arrhythmias in dogs.
Allen, JD; Harron, DW; Kerr, MJ; Shanks, RG,
)
1.93
"Encainide is a new antiarrhythmic class IC agent. "( Electrophysiological effects of encainide and its metabolites in 11 patients.
Caron, JF; Kacet, S; Kher, AR; Lekieffre, JP; Libersa, CC; Pladys, AM; Poirier, JM,
)
1.86
"Encainide is a potent sodium channel antagonist. "( Basic and clinical cardiac electrophysiology of encainide.
Mason, JW, 1986
)
1.97
"Encainide is a class IC antiarrhythmic agent having little or no effect on action-potential duration or maximum diastolic potential but decreasing the maximum rate of phase O depolarization as well as increasing atrial and ventricular effective refractory periods. "( Encainide.
Antonaccio, MJ; Byrne, JE; Gomoll, AW, 1989
)
3.16
"Encainide appears to be a safe and effective antiarrhythmic agent with few adverse effects and negligible hemodynamic effects."( Encainide: a new antiarrhythmic agent.
Thomas, RL; Wehmeyer, AE, 1986
)
2.44
"Encainide is a class IC agent possessing a broad spectrum of antiarrhythmic actions in a variety of animal models. "( Electrophysiology, hemodynamic and arrhythmia efficacy model studies on encainide.
Antonaccio, MJ; Byrne, JE; Gomoll, AW, 1986
)
1.95
"Encainide is a potent new antiarrhythmic agent with 2 major active metabolites and 2 distinct phenotypes for metabolism, extensive (approximately 92%) and nonextensive (8%). "( Relation of blood level and metabolites to the antiarrhythmic effectiveness of encainide.
Harrison, DC; Kates, RE; Quart, BD, 1986
)
1.94
"Encainide appears to be a useful antiarrhythmic agent."( Encainide in lethal ventricular arrhythmias evaluated by electrophysiologic testing and decrease in symptoms.
Horowitz, LN, 1986
)
2.44
"Encainide is an antiarrhythmic drug with class IC activity which has been used in the treatment of life-threatening ventricular arrhythmias, symptomatic ventricular arrhythmias and supraventricular arrhythmias. "( Encainide. A review of its pharmacological properties and therapeutic efficacy.
Brogden, RN; Todd, PA, 1987
)
3.16
"Encainide is a class IC antiarrhythmic agent that has been under clinical investigation for the last decade. "( Encainide: its electrophysiologic and antiarrhythmic effects, pharmacokinetics, and safety.
Estes, NA; Tordjman, T, 1987
)
3.16
"Encainide is an effective and safe agent for treating atrial fibrillation in patients with Wolff-Parkinson-White syndrome."( Encainide for atrial fibrillation associated with Wolff-Parkinson-White syndrome.
Dougherty, AH; Heger, JJ; Markel, ML; Miles, WM; Naccarelli, GV; Prystowsky, EN; Rinkenberger, RL; Zipes, DP, 1988
)
2.44
"Encainide is an effective and well-tolerated drug to prevent recurrence of AVRT in patients with Wolff-Parkinson-White syndrome."( Encainide for treatment of atrioventricular reciprocating tachycardia in the Wolff-Parkinson-White syndrome.
Dougherty, AH; Heger, JJ; Markel, ML; Miles, WM; Naccarelli, GV; Prystowsky, EN; Rinkenberger, RL; Zipes, DP, 1988
)
2.44
"Encainide is a type Ic antiarrhythmic agent. "( Marked Q-T prolongation due to encainide therapy.
Davies, W; Jazayeri, M; Tchou, P, 1988
)
2
"Encainide is a benzanilide derivative that is effective against ventricular arrhythmias but, at times, may be arrhythmogenic. "( Effects of encainide on the determinants of cardiac excitability in sheep Purkinje fibers.
Arnsdorf, MF; Sawicki, GJ; Schmidt, GA, 1985
)
2.1

Effects

Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives. It has a very favorable safety profile for use in the treatment of supraventricular arrhythmias.

Encainide hydrochloride has distinct electrophysiologic properties that suggest active antiarrhythmic properties. Encainide has no significant effect on the normal sinoatrial node, and only its metabolites significantly depress atrioventricular nodal conduction and refractoriness.

ExcerptReferenceRelevance
"Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives."( Encainide: its electrophysiologic and antiarrhythmic effects, pharmacokinetics, and safety.
Estes, NA; Tordjman, T, 1987
)
2.44
"Encainide has a very favorable safety profile for use in the treatment of supraventricular arrhythmias."( Safety considerations and dosing guidelines for encainide in supraventricular arrhythmias.
Soyka, LF, 1988
)
1.25
"Encainide has no significant effect on the normal sinoatrial node, and only its metabolites significantly depress atrioventricular nodal conduction and refractoriness."( Basic and clinical cardiac electrophysiology of encainide.
Mason, JW, 1986
)
1.25
"As encainide itself has intrinsic antiarrhythmic activity at these concentrations, this generally results in the desired clinical response."( Oxidative metabolism of encainide: polymorphism, pharmacokinetics and clinical considerations.
Aslanian, WS; McAllister, CB; Wilkinson, GR; Wolfenden, HT; Woosley, RL, 1986
)
1.09
"Encainide has been given for up to 2 years in 140 patients with sustained ventricular tachycardia or ventricular fibrillation."( Relation of blood level and metabolites to the antiarrhythmic effectiveness of encainide.
Harrison, DC; Kates, RE; Quart, BD, 1986
)
1.22
"Encainide has been used to treat 230 patients with supraventricular arrhythmias, including patients with reentry supraventricular tachycardia of the atrioventricular reentry (Wolff-Parkinson-White syndrome) and the atrioventricular nodal reentry types associated with atrial fibrillation, paroxysmal supraventricular tachycardia or both, as well as incessant supraventricular tachycardia. "( Treatment of supraventricular arrhythmias with encainide.
Pool, PE, 1986
)
1.97
"Encainide hydrochloride has distinct electrophysiologic properties that suggest active antiarrhythmic properties. "( Encainide in lethal ventricular arrhythmias evaluated by electrophysiologic testing and decrease in symptoms.
Horowitz, LN, 1986
)
3.16
"Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives."( Encainide: its electrophysiologic and antiarrhythmic effects, pharmacokinetics, and safety.
Estes, NA; Tordjman, T, 1987
)
2.44
"Encainide has a very favorable safety profile for use in the treatment of supraventricular arrhythmias."( Safety considerations and dosing guidelines for encainide in supraventricular arrhythmias.
Soyka, LF, 1988
)
1.25

Actions

Encainide can cause adverse hemodynamic and clinical effects in patients with severe chronic heart failure. Encainide could enhance excitability by increasing membrane and slope resistance without altering the nonlinearities of the current-voltage relationship.

ExcerptReferenceRelevance
"Encainide can cause adverse hemodynamic and clinical effects in patients with severe chronic heart failure."( Adverse hemodynamic and clinical effects of encainide in severe chronic heart failure.
Gottlieb, SS; Kukin, ML; Medina, N; Packer, M; Yushak, M, 1989
)
1.98
"With encainide, the percent increase in PR, QRS and QT interval duration was, respectively: 32.7 (p less than 0.001), 30.8 (p less than 0.001) and 10.6% (p less than 0.01)."( Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: a double-blind placebo-controlled crossover study.
Caron, JF; Dupuis, BA; Kacet, S; Kher, AR; Lekieffre, JP; Libersa, CC; Poirier, JM; Wanszelbaum, H, 1985
)
1.04
"Encainide could enhance excitability by increasing membrane and slope resistance without altering the nonlinearities of the current-voltage relationship despite an actual depression of the sodium system."( Effects of encainide on the determinants of cardiac excitability in sheep Purkinje fibers.
Arnsdorf, MF; Sawicki, GJ; Schmidt, GA, 1985
)
1.38

Treatment

ExcerptReferenceRelevance
"Encainide treatment in patients after myocardial infarction is associated with increased risk of sudden cardiac death. "( Proarrhythmia of a class Ic drug: suppression by combination with a drug prolonging repolarization in the dog late after infarction.
Duff, HJ; Laganiere, S; Lester, W; Rude, E; Stemler, M; Thannhauser, T, 1995
)
1.73

Toxicity

ExcerptReferenceRelevance
"Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents."( Effects of advancing age on the efficacy and side effects of antiarrhythmic drugs in post-myocardial infarction patients with ventricular arrhythmias. The CAST Investigators.
Akiyama, T; Barker, AH; Campbell, WB; Friedman, L; Josephson, RA; Keller, M; Papa, L; Pawitan, Y; Rubbert, P, 1992
)
0.28
"The safety of encainide has been evaluated using retrospective analyses of the Bristol-Myers Supraventricular and Ventricular Arrhythmias data base and of the Post-Marketing Adverse Experience Report data and prospective analyses of the Cardiac Arrhythmia Suppression Trial (CAST), the Cardiac Arrhythmia Pilot Study (CAPS), and the Ventricular Tachycardia/Heart Disease and Boston studies."( Encainide--an updated safety profile.
Thomis, JA, 1990
)
2.08
" The profile of drug-related adverse effects was comparable to that previously reported, causing discontinuance in 6% of patients."( Safety considerations and dosing guidelines for encainide in supraventricular arrhythmias.
Soyka, LF, 1988
)
0.53
" In all instances adverse effects emerged before ectopic activity was suppressed satisfactorily prohibiting further increment of dosage."( Increased incidence of side effects after encainide: a newly developed antiarrhythmic drug.
Berchtold-Kanz, E; Hust, M; Just, H; Nitsche, K; Schwarz, G, 1984
)
0.53
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32

Pharmacokinetics

The pharmacodynamic characteristics of 3-methoxy-O-demethyl encainide (MODE) were studied in instrumented, chloralose-anesthetized dogs. In this population, quinidine significantly increased encainides elimination half-life from 1 to 2.

ExcerptReferenceRelevance
" The antipyrine half-life was significantly longer and clearance was significantly lower in patients with cirrhosis."( Pharmacokinetics of encainide in patients with cirrhosis.
Hoensch, HP; Mönig, H; Ohnhaus, EE; Wensing, G, 1991
)
0.6
"The pharmacodynamic characteristics of 3-methoxy-O-demethyl encainide (MODE) were studied in instrumented, chloralose-anesthetized dogs."( Pharmacodynamic modeling of antiarrhythmic drug effects--application to 3-methoxy-O-demethyl encainide.
Davy, JM; Dorian, P; Kates, RE,
)
0.59
" Data from in vitro and animal studies have indicated that MODE has electrophysiologic and pharmacokinetic features that make its further evaluation desirable; in earlier studies, we found that MODE suppressed chronic high-frequency nonsustained ventricular arrhythmias at plasma concentrations of 50-160 ng/ml."( Antiarrhythmic efficacy, clinical electrophysiology, and pharmacokinetics of 3-methoxy-O-desmethyl encainide (MODE) in patients with inducible ventricular tachycardia or fibrillation.
Echt, DS; Lee, JT; Roden, DM; Woosley, RL, 1989
)
0.49
" On the other hand, the elimination half-life of antiarrhythmic agents that have a large volume of distribution and are highly cleared by the liver may be twice as long in patients with CHF compared with normal subjects."( Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents.
Echt, DS; Roden, DM; Woosley, RL, 1986
)
0.27
"This article reviews clinical pharmacokinetic data on 8 new antiarrhythmic agents."( Clinical pharmacokinetics of the newer antiarrhythmic agents.
Gillis, AM; Kates, RE,
)
0.13
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35

Compound-Compound Interactions

ExcerptReferenceRelevance
"Antiarrhythmic and electrophysiological effects of three class I antiarrhythmic agents, one from each subclass A, B, and C, were assessed in single use and in combination with amiodarone in patients with inducible, sustained ventricular tachycardia that was not suppressed by monotherapy with these agents."( A prospective comparison of class IA, B, and C antiarrhythmic agents in combination with amiodarone in patients with inducible, sustained ventricular tachycardia.
Kadish, A; Morady, F; Toivonen, L, 1991
)
0.28
"Class I antiarrhythmic agents slow ventricular conduction and increase ventricular refractoriness when used in combination with amiodarone."( A prospective comparison of class IA, B, and C antiarrhythmic agents in combination with amiodarone in patients with inducible, sustained ventricular tachycardia.
Kadish, A; Morady, F; Toivonen, L, 1991
)
0.28
" We examined the efficacy and electrophysiology of 110 antiarrhythmic drug combination trials at electrophysiologic study in 74 patients with recurrent ventricular tachycardia."( Antiarrhythmic drug combinations in the treatment of ventricular tachycardia.
Echt, DS; Griffin, JC; Keefe, DL; Mason, JW; Ross, DL; Swerdlow, CD; Sze, DY; Winkle, RA, 1982
)
0.26

Bioavailability

Enainide disposition is complex with variable bioavailability and active metabolites that contribute substantially to activity. In the EM group, the oral bioavailability of encainide was only about 25 to 30% because of extensive presystemic (first-pass) metabolism. No accumulation occurred after multiple oral dosing with 50 mg every 8 hr for 3 days.

ExcerptReferenceRelevance
"The bioavailability of drugs that undergo extensive presystemic hepatic metabolism may be increased by concomitant ingestion with food."( Impact of food on the bioavailability of encainide.
Destache, CJ; Hilleman, DE; Malesker, MA; Mohiuddin, SM; Nipper, HC; Stoysich, AM, 1992
)
0.55
" Thus, encainide bioavailability was increased in cirrhosis."( Pharmacokinetics of encainide in patients with cirrhosis.
Hoensch, HP; Mönig, H; Ohnhaus, EE; Wensing, G, 1991
)
1.06
" Over 90% of patients are extensive metabolizers (EM) in whom the oral bioavailability of encainide is only 30% because of extensive first-pass metabolism."( Pharmacokinetics and metabolism of encainide.
Jaillon, P, 1990
)
0.78
" Absorption is essentially complete, but bioavailability is variable because of first-pass metabolism."( Encainide: a new antiarrhythmic agent.
Thomas, RL; Wehmeyer, AE, 1986
)
1.71
" Bioavailability of encainide ranges from 7% to 82%, whereas that of flecainide is 90% to 95%."( Encainide hydrochloride and flecainide acetate: two class 1c antiarrhythmic agents.
Chase, SL; Sloskey, GE, 1987
)
2.04
" Flecainide pharmacokinetics are suitable for oral use but encainide disposition is complex with variable bioavailability and active metabolites that contribute substantially to activity."( Clinical profiles of newer class I antiarrhythmic agents--tocainide, mexiletine, encainide, flecainide and lorcainide.
Pottage, A, 1983
)
0.74
" Lorcainide is also a class Ic antiarrhythmic drug, the bioavailability of which is nonlinear."( Clinical pharmacokinetics of the newer antiarrhythmic agents.
Gillis, AM; Kates, RE,
)
0.13
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."( QSAR model for drug human oral bioavailability.
Topliss, JG; Yoshida, F, 2000
)
0.31
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36

Dosage Studied

Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%) patients. No patient had syncope or required cardioversion while receiving the drug.

ExcerptRelevanceReference
" Prehospital care providers must be aware that apparently trivial amounts of some adult dosage forms can be toxic to small children."( Encainide overdose in an infant.
Bolon, CE; Cassidy, S; Kelley, MT; Mortensen, ME; Walson, PD, 1992
)
1.73
" Decreased clearance in patients with renal dysfunction necessitates a reduction in dosage to avoid toxic and dose-related proarrhythmic effects."( Encainide dosing in patients with severe renal dysfunction: report of a case and literature review.
Fronc, H; Hessen, SE; Kutalek, SP; Nydegger, CC; Porter, RS, 1992
)
1.73
" Twenty-four-hour ambulatory ECGs were obtained at baseline for each daily dosage of 75 mg, 150 mg, and 225 mg of encainide during the in-hospital titration period and at the end of the first and sixth months during the follow-up period."( Long-term efficacy and safety of oral encainide in the treatment of chronic ventricular ectopic activity: relationship to plasma concentrations--a French multicenter trial.
Barnay, C; Cheymol, G; Coumel, P; Dumoulin, P; Flammang, D; Jaillon, P; Kher, A; Medvedowsky, JL; Poirier, JM; Valty, J, 1985
)
0.75
"9 years with a mean dosage of 156 mg/day."( Treatment of ectopic atrial arrhythmias and premature atrial complexes in adults with encainide.
Pool, PE; Quart, BD, 1988
)
0.5
"The effect of encainide on chronic pacing thresholds was evaluated in 10 patients, age 64-89, who were exposed to weekly increased encainide dosing (25 mg TID, 50 mg TID, 75 mg TID)."( Effects of encainide on the function of implanted pacemakers.
Pool, PE; Salel, AF; Seagren, SC, 1989
)
1.03
" However, because no change occurs in the systemic exposure to the active metabolites, dosage adjustments in extensive metabolizers are probably not required for patients receiving combination encainide and diltiazem therapy."( The effect of diltiazem on the disposition of encainide and its active metabolites.
Bottorff, MB; Hoon, TJ; Kazierad, DJ; Lalonde, RL; Mirvis, DM, 1989
)
0.72
" Its dosage and role in antiarrhythmic therapy are discussed."( Encainide.
Antonaccio, MJ; Byrne, JE; Gomoll, AW, 1989
)
1.72
" Serious adverse reactions necessitate a change in antiarrhythmic therapy, as opposed to lowering drug dosage to an ineffective level."( Antiarrhythmic drug therapy. Recent advances and current status.
Somberg, J, 1985
)
0.27
" Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required."( Drug interaction studies and encainide use in renal and hepatic impairment.
Gallo, DG; Quart, BD; Sami, MH; Wood, AJ, 1986
)
0.56
" During a double-blind drug and dose selection phase, investigators were permitted to change drug or dosage to achieve greater than or equal to 70% suppression in VPC frequency and greater than 90% suppression of runs of VPC with the exception of patients assigned to placebo, who continued receiving it."( Effects of encainide, flecainide, imipramine and moricizine on ventricular arrhythmias during the year after acute myocardial infarction: the CAPS.
, 1988
)
0.66
"A multicenter, 2-week, double-blind, placebo-controlled, parallel group study was performed to determine the dose-response relation of encainide administered 3 times daily and to determine its onset of action."( Dose-response range of encainide for benign and potentially lethal ventricular arrhythmias.
Clark, DM; Hsu, PH; Lee, I; Miller, R; Morganroth, J; Pool, P, 1986
)
0.79
" After chronic dosing to steady state, quantitatively similar changes were seen."( Encainide disposition in patients with renal failure.
Bergstrand, RH; Roden, DM; Stone, WJ; Wang, T; Wilkinson, GR; Wolfenden, HT; Wood, AJ; Woosley, RL, 1986
)
1.71
" However, because no change occurs in the levels of the pharmacologically active metabolites, dosage adjustment is probably not required in patients with cirrhosis."( Encainide disposition in patients with chronic cirrhosis.
Avant, GR; Bergstrand, RH; Roden, DM; Siddoway, LA; Sutton, WW; Wang, T; Wilkinson, GR; Wolfenden, H; Wood, AJ; Woosley, RL, 1986
)
1.71
" Three-times-a-day dosing was as effective as 4-times-a-day dosing."( Dosing recommendations for encainide.
Antonaccio, MJ; Verjee, S, 1986
)
0.57
" Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%), and no patient had syncope or required cardioversion while receiving the drug."( Encainide for treatment of supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome.
Fineberg, N; Heger, JJ; Markel, ML; Miles, WM; Prystowsky, EN; Zipes, DP, 1986
)
2.62
" When the flecainide dosage for patients with lethal ventricular arrhythmias was chosen using steady-state pharmacologic principles, the occurrence of all proarrhythmic events and deaths dropped from 26% and 13% to 10% and 0%, respectively."( Risk factors for the development of proarrhythmic events.
Morganroth, J, 1987
)
0.27
"The chemistry, electrophysiology, pharmacokinetics, clinical use and efficacy, adverse effects, drug interactions, and dosage of encainide hydrochloride and flecainide acetate are reviewed."( Encainide hydrochloride and flecainide acetate: two class 1c antiarrhythmic agents.
Chase, SL; Sloskey, GE, 1987
)
1.92
" There was no difference in age or encainide dosage between hyperglycemic and nonhyperglycemic patients."( Encainide-induced hyperglycemia.
Fifield, J; Hodges, M; Krejci, J; Salerno, DM, 1988
)
1.99
" Encainide biotransformation is impaired in hepatic disease, but no major dosage changes are required."( Clinical pharmacokinetics of encainide.
Roden, DM; Woosley, RL, 1988
)
1.48
" Thus E is highly effective in the prevention of PSVT; the drug seems well tolerated thanks to the low dosage required for the control of PSVT."( [Intravenous and oral encainide: electrophysiological effects in patients with paroxysmal reciprocating supraventricular tachycardia].
Bianchi, PE; Bobba, P; Chimienti, M; Klersy, C; Marangoni, E; Moizi, M; Montemartini, C; Previtali, M; Salerno, JA, 1985
)
0.58
" If side effects intervene that may cause continued therapy to be intolerable, changing the antiarrhythmic agent, as opposed to decreasing the dosage to an ineffective range, may be appropriate."( New directions in antiarrhythmic drug therapy.
Somberg, JC, 1984
)
0.27
"Measurement of drug levels is becoming increasingly popular to optimise the dosage of various drugs."( Reliability of antiarrhythmic drug plasma concentration monitoring.
Follath, F; Ganzinger, U; Schuetz, E,
)
0.13
" (radiolabeled) and single and multiple oral (nonradiolabeled) dosing to two groups of normal subjects characterized as "poor" (PM) and "extensive" (EM) metabolizers of debrisoquine."( Influence of genetic polymorphism on the metabolism and disposition of encainide in man.
Roden, DM; Wang, T; Wilkinson, GR; Wolfenden, HT; Wood, AJ; Woosley, RL, 1984
)
0.5
" The dosage of encainide was increased from 25 to 75 mg three times daily and the antiarrhythmic effect monitored by repeated 24-h Holter registration and in some patients by treadmill exercise testing."( Increased incidence of side effects after encainide: a newly developed antiarrhythmic drug.
Berchtold-Kanz, E; Hust, M; Just, H; Nitsche, K; Schwarz, G, 1984
)
0.88
" 3 On a dosage basis, encainide was seven times, lorcainide fourteen times and ORG 6001 twice as potent as lignocaine in raising VFT."( Antifibrillatory efficacy of encainide, loracainide and ORG 6001 compared with lignocaine in isolated hearts of rabbits and guinea-pigs.
Almotrefi, AA; Baker, JB, 1981
)
0.87
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
anti-arrhythmia drugA drug used for the treatment or prevention of cardiac arrhythmias. Anti-arrhythmia drugs may affect the polarisation-repolarisation phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibres.
sodium channel blockerAn agent that inhibits sodium influx through cell membranes.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
piperidines
benzamides
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (67)

Assay IDTitleYearJournalArticle
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID74038Effective dose in vivo for cardiac refractoriness (ERP) using paced guinea pig model1993Journal of medicinal chemistry, Oct-29, Volume: 36, Issue:22
4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: novel antiarrhythmic agents.
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID28681Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID29812Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1222793Dissociation constant, pKa of the compound2013Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5
Which metabolites circulate?
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID27167Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID161144Percentage inhibition of specific binding of [3H]dofetilide (UK-68,798) from cardiac myocytes with blockade of delayed rectifier K+ channel1993Journal of medicinal chemistry, Oct-29, Volume: 36, Issue:22
4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: novel antiarrhythmic agents.
AID29359Ionization constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID205279Percentage inhibition of specific binding of [3H]batrachotoxin [3H]BTX) in sodium channel from cardiac myocytes at 10 uM1993Journal of medicinal chemistry, Oct-29, Volume: 36, Issue:22
4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: novel antiarrhythmic agents.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID78122In vivo index of cardiac contractility using paced guinea pig model1993Journal of medicinal chemistry, Oct-29, Volume: 36, Issue:22
4,5-Dihydro-1-phenyl-1H-2,4-benzodiazepines: novel antiarrhythmic agents.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (330)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990212 (64.24)18.7374
1990's107 (32.42)18.2507
2000's6 (1.82)29.6817
2010's5 (1.52)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 31.67

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index31.67 (24.57)
Research Supply Index6.05 (2.92)
Research Growth Index3.94 (4.65)
Search Engine Demand Index47.56 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (31.67)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials74 (21.14%)5.53%
Reviews61 (17.43%)6.00%
Case Studies24 (6.86%)4.05%
Observational0 (0.00%)0.25%
Other191 (54.57%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
[NCT00000504]Phase 20 participants Interventional1982-09-30Completed
[NCT00000526]Phase 30 participants Interventional1986-08-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]