U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C21H29N3O
Molecular Weight 339.4753
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DISOPYRAMIDE

SMILES

CC(C)N(CCC(c1ccccc1)(c2ccccn2)C(=N)O)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 339.4753
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
[Torsades de pointes ventricular tachycardia induced by disopyramide at therapeutic serum concentration].
1992 Aug 20
Acquired long QT syndrome due to antiarrhythmic drugs and bradyarrhythmias.
1992 Jan 27
Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.
1999 Apr
Torsades de pointes due to drug interaction between disopyramide and clarithromycin.
1999 Sep-Oct
Comparative safety of the different macrolides.
2001
Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy.
2001 Apr
Disopyramide-induced pneumonitis, diagnosed by lymphocyte stimulation test using bronchoalveolar lavage fluid.
2001 Aug
Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits.
2001 Dec
Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide.
2001 Feb
Inhibition of HERG potassium channel current by the class 1a antiarrhythmic agent disopyramide.
2001 Feb 9
Disopyramide and its metabolite enhance insulin release from clonal pancreatic beta-cells by blocking K(ATP) channels.
2001 Jan
The effects of flecainide on ATP-sensitive K(+) channels in pig urethral myocytes.
2001 Jul
Role of biantennary glycans and genetic variants of human alpha1-acid glycoprotein in enantioselective binding of basic drugs as studied by high performance frontal analysis/capillary electrophoresis.
2001 Mar
Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.
2001 Nov
Drug block of I(kr): model systems and relevance to human arrhythmias.
2001 Nov
[Acute intoxication with disopyramide: case report with literature review].
2001 Nov-Dec
Disopyramide: interactions with marcolide antibiotics.
2001 Oct
Enantioselective binding of disopyramide to alpha1-acid glycoprotein and its variants.
2001 Oct
Use of beta-blockers in 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
Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities.
2002 Dec
An intraoperative diagnosis of dynamic left ventricular outflow tract obstruction using transesophageal echocardiography leads to the treatment with intravenous disopyramide.
2002 Feb
What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers.
2002 Nov
[Anti-arrhythmic therapy: diagnostic possibilities of signal-averaged electrocardiography and heart rate variability].
2003
Capillary electrophoretic study on pH dependence of enantioselective disopyramide binding to genetic variants of human alpha1-acid glycoprotein.
2003 Aug
Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.
2003 Dec 16
Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians.
2003 Dec 16
Abnormal response to sodium channel blockers in patients with Brugada syndrome: augmented localised wall motion abnormalities in the right ventricular outflow tract region detected by electron beam computed tomography.
2003 Feb
Inhibitory effect of erythromycin on potassium currents in rat ventricular myocytes in comparison with disopyramide.
2003 Jul
Interaction of quinidine, disopyramide and metoprolol with melanin in vitro in relation to drug-induced ocular toxicity.
2003 Jul
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
Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes.
2003 Mar
Interactions between grapefruit juice and cardiovascular drugs.
2004
Atrial fibrillation: rate control often better than rhythm control.
2004 Apr
Recurrent syncopic episodes as a consequence of combined Brugada syndrome and paroxysmal atrial fibrillation. Which is the therapy of choice?
2004 Apr
Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.
2004 Dec
Antiarrhythmic drug therapy of atrial fibrillation.
2004 Feb
Theoretical possibilities for the development of novel antiarrhythmic drugs.
2004 Jan
Effects of class I antiarrhythmic drugs on the digitalis-induced triggered activity arrhythmia model: a rationale for the short-term use of class I drugs against triggered arrhythmias.
2004 Jan
Effects of antiarrhythmic agents on left ventricular function during exercise in patients with chronic left ventricular dysfunction.
2004 May
Failure of disopyramide to improve right ventricular outflow tract obstruction after living-donor lobar lung transplantation.
2004 Nov
Pharmacological treatment of reflex syncope.
2004 Oct
Acute ventricular rate control in atrial fibrillation and atrial flutter.
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
Toxic interactions between fluconazole and disopyramide in chick embryos.
2005 Jan
Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone.
2005 Jan
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 Jun 25 21:14:04 UTC 2021
Edited
by admin
on Fri Jun 25 21:14:04 UTC 2021
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
.ALPHA.-(2-(DIISOPROPYLAMINO)ETHYL)-.ALPHA.-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 [EP MONOGRAPH]
Common Name English
DISOPYRAMIDE [WHO-DD]
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 Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
NCI_THESAURUS C47793
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
NDF-RT N0000175426
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
LIVERTOX 316
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
WHO-VATC QC01BA03
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
NCI_THESAURUS C93038
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
Code System Code Type Description
CAS
3737-09-5
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
DRUG BANK
DB00280
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
MESH
D004206
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
PUBCHEM
3114
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
EPA CompTox
3737-09-5
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
NCI_THESAURUS
C61730
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
WIKIPEDIA
DISOPYRAMIDE
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
RXCUI
3541
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
926
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
EVMPD
SUB07237MIG
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
ChEMBL
CHEMBL517
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
CAS
74427-45-5
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
SUPERSEDED
INN
1307
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
ECHA (EC/EINECS)
223-110-2
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
LACTMED
Disopyramide
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
MERCK INDEX
M4672
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY Merck Index
IUPHAR
7167
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
FDA UNII
GFO928U8MQ
Created by admin on Fri Jun 25 21:14:04 UTC 2021 , Edited by admin on Fri Jun 25 21:14:04 UTC 2021
PRIMARY
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