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Details

Stereochemistry RACEMIC
Molecular Formula C21H29N3O
Molecular Weight 339.4745
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DISOPYRAMIDE

SMILES

CC(C)N(CCC(C(N)=O)(C1=CC=CC=C1)C2=CC=CC=N2)C(C)C

InChI

InChIKey=UVTNFZQICZKOEM-UHFFFAOYSA-N
InChI=1S/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25)

HIDE SMILES / InChI

Molecular Formula C21H29N3O
Molecular Weight 339.4745
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/disopyramide.html

Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs. Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors. It is used for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.

Originator

Curator's Comment: Introduced as Rythmodan by Cassenne, France, in 1969

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
52.5 µM [IC50]
Target ID: KATP channels, Mus musculus
4.8 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DISOPYRAMIDE PHOSPHATE

Approved Use

indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening.

Launch Date

4.7779201E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.08 mg/L
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DISOPYRAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
27.1 μg × h/mL
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DISOPYRAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.8 h
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DISOPYRAMIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DISOPYRAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
35%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DISOPYRAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
432 mg 1 times / day steady, oral (median)
Dose: 432 mg, 1 times / day
Route: oral
Route: steady
Dose: 432 mg, 1 times / day
Sources:
unhealthy, 47 + 20 years
n = 118
Health Status: unhealthy
Condition: obstructive hypertrophic cardiomyopathy
Age Group: 47 + 20 years
Sex: M+F
Population Size: 118
Sources:
Disc. AE: Dry mouth, Prostatism...
AEs leading to
discontinuation/dose reduction:
Dry mouth (7%)
Prostatism (7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Dry mouth 7%
Disc. AE
432 mg 1 times / day steady, oral (median)
Dose: 432 mg, 1 times / day
Route: oral
Route: steady
Dose: 432 mg, 1 times / day
Sources:
unhealthy, 47 + 20 years
n = 118
Health Status: unhealthy
Condition: obstructive hypertrophic cardiomyopathy
Age Group: 47 + 20 years
Sex: M+F
Population Size: 118
Sources:
Prostatism 7%
Disc. AE
432 mg 1 times / day steady, oral (median)
Dose: 432 mg, 1 times / day
Route: oral
Route: steady
Dose: 432 mg, 1 times / day
Sources:
unhealthy, 47 + 20 years
n = 118
Health Status: unhealthy
Condition: obstructive hypertrophic cardiomyopathy
Age Group: 47 + 20 years
Sex: M+F
Population Size: 118
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​

Drug as perpetrator​

Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Acquired long QT syndrome due to antiarrhythmic drugs and bradyarrhythmias.
1992 Jan 27
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.
1992 Nov
Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.
1999 Apr
Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans.
2000 Aug
Potentially fatal interaction between azithromycin and disopyramide.
2000 Sep
Comparative safety of the different macrolides.
2001
Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy.
2001 Apr
The effects of flecainide on ATP-sensitive K(+) channels in pig urethral myocytes.
2001 Jul
Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.
2001 Nov
Enantioselective binding of disopyramide to alpha1-acid glycoprotein and its variants.
2001 Oct
Use of beta-blockers in atrial fibrillation.
2002
Strategy for the management of vasovagal syncope.
2002
Risk of mortality in a cohort of patients newly diagnosed with chronic atrial fibrillation.
2002
[Role amiodarone in sinus rhythm maintenance after successful cardioversion in patients with chronic non-valvular atrial fibrillation].
2002 Dec
MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs.
2002 Dec
Effects of disopyramide and mexiletine on the terminal repolarization process of the in situ heart assessed using the halothane-anesthetized in vivo canine model.
2002 Sep
Maintaining stability of sinus rhythm in atrial fibrillation: antiarrhythmic drugs versus ablation.
2002 Sep
Effects of orthostatic self-training on head-up tilt testing for the prevention of tilt-induced neurocardiogenic syncope: comparison of pharmacological therapy.
2003 Apr
Capillary electrophoretic study on pH dependence of enantioselective disopyramide binding to genetic variants of human alpha1-acid glycoprotein.
2003 Aug
The effect of commonly used drugs on angiogenesis.
2003 Jan-Feb
[Drug therapy of atrial fibrillation].
2003 Jun 15
Safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications in patients with atrial fibrillation or atrial flutter.
2003 Jun 15
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
[Drug binding analysis of human alpha 1-acid glycoprotein using capillary electrophoresis].
2003 Sep
Accuracy of calculated pH-dependent aqueous drug solubility.
2004 Aug
Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.
2004 Dec
Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.
2004 Jan
Pharmacological treatment of reflex syncope.
2004 Oct
Myocardial bundles with slow conduction properties are present on the left interventricular septal surface of normal human hearts.
2004 Sep
Human organic cation transporter 3 mediates the transport of antiarrhythmic drugs.
2004 Sep 19
Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring.
2005 Feb
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.
2005 Feb
Patents

Sample Use Guides

Usual Adult Dose for Arrhythmias 400-800 mg/day. The recommended dose for most adults is 600 mg/day. Patients < 50 kg may be given 400 mg/day.
Route of Administration: Oral
Disopyramide (10-100 uM) led to increases in the action potential duration (APD) at 90% repolarization level in rat ventricular myocytes.
Substance Class Chemical
Created
by admin
on Fri Dec 16 22:45:07 UTC 2022
Edited
by admin
on Fri Dec 16 22:45:07 UTC 2022
Record UNII
GFO928U8MQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DISOPYRAMIDE
EP   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
DISOPYRAMIDE [USAN]
Common Name English
(±)-DISOPYRAMIDE
Common Name English
LISPINE
Brand Name English
2-PYRIDINEACETAMIDE, .ALPHA.-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-.ALPHA.-PHENYL-
Systematic Name English
DISOPYRAMIDE [VANDF]
Common Name English
DISOPYRAMIDE [MART.]
Common Name English
RYTHMODAN P
Brand Name English
?-[2-(Diisopropylamino)ethyl]-?-phenyl-2-pyridineacetamide
Systematic Name English
4-DIISOPROPYLAMINO-2-PHENYL-2-(2-PYRIDYL)BUTYRAMIDE
Systematic Name English
DICORANTIL
Brand Name English
RITMILEN
Brand Name English
SEARLE-703
Common Name English
DISOPYRAMIDE [JAN]
Common Name English
SC-7031
Code English
Disopyramide [WHO-DD]
Common Name English
DISOPYRAMIDE [EP MONOGRAPH]
Common Name English
ISORYTHM
Brand Name English
DL-DISOPYRAMIDE
Common Name English
DISOPYRAMIDE [MI]
Common Name English
disopyramide [INN]
Common Name English
(RS)-DISOPYRAMIDE
Common Name English
H-3292
Code English
Classification Tree Code System Code
WHO-ATC C01BA03
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
NCI_THESAURUS C47793
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
NDF-RT N0000175426
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
LIVERTOX NBK548693
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
WHO-VATC QC01BA03
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
NCI_THESAURUS C93038
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
Code System Code Type Description
CAS
3737-09-5
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
DRUG BANK
DB00280
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
MESH
D004206
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
PUBCHEM
3114
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
EPA CompTox
DTXSID1045536
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
NCI_THESAURUS
C61730
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
WIKIPEDIA
DISOPYRAMIDE
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
DAILYMED
GFO928U8MQ
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
RXCUI
3541
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY RxNorm
CHEBI
4657
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
DRUG CENTRAL
926
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
EVMPD
SUB07237MIG
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
ChEMBL
CHEMBL517
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
CAS
74427-45-5
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
SUPERSEDED
INN
1307
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
ECHA (EC/EINECS)
223-110-2
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
LACTMED
Disopyramide
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
MERCK INDEX
M4672
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY Merck Index
IUPHAR
7167
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
FDA UNII
GFO928U8MQ
Created by admin on Fri Dec 16 22:45:07 UTC 2022 , Edited by admin on Fri Dec 16 22:45:07 UTC 2022
PRIMARY
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