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

Details

Stereochemistry RACEMIC
Molecular Formula C21H29N3O.H3O4P
Molecular Weight 437.4705
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DISOPYRAMIDE PHOSPHATE

SMILES

CC(C)N(CCC(c1ccccc1)(c2ccccn2)C(=N)O)C(C)C.OP(=O)(O)O

InChI

InChIKey=CGDDQFMPGMYYQP-UHFFFAOYSA-N
InChI=1S/C21H29N3O.H3O4P/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;1-5(2,3)4/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25);(H3,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.
1992 Nov
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
Effective disopyramide treatment in a boy with mid-ventricular hypertrophic obstructive cardiomyopathy.
2002 Jul
[Antiarrhythmic drugs in atrial fibrillation].
2002 Jun 15
What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers.
2002 Nov
Development and use of a computer program to detect potentially inappropriate prescribing in older adults residing in Canadian long-term care facilities.
2002 Oct 14
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
[Anti-arrhythmic therapy: diagnostic possibilities of signal-averaged electrocardiography and heart rate variability].
2003
[Comparison of the efficacies of disopyramide, cibenzoline and aprindine for the termination of paroxysmal and persistent atrial fibrillation in elderly and non-elderly patients].
2003 Apr
Capillary electrophoretic study on pH dependence of enantioselective disopyramide binding to genetic variants of human alpha1-acid glycoprotein.
2003 Aug
Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.
2003 Aug 18
Ropivacaine combined with various anti-arrhythmic drugs results in mild alterations in myocardial contractility in pigs.
2003 Dec
Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.
2003 Dec 16
Hypertrophic obstructive cardiomyopathy: mechanism of obstruction and response to therapy.
2003 Fall
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
The effect of commonly used drugs on angiogenesis.
2003 Jan-Feb
Inhibitory effect of erythromycin on potassium currents in rat ventricular myocytes in comparison with disopyramide.
2003 Jul
Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage.
2003 Jun
Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamide.
2003 Jun 27
Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes.
2003 Mar
[Relationship between duration of arrhythmia and subsequent preventive effect of disopyramide after cardioversion in patients with symptomatic paroxysmal and persistent atrial fibrillation].
2003 Sep
[Drug binding analysis of human alpha 1-acid glycoprotein using capillary electrophoresis].
2003 Sep
Randomized clinical trials of neurally mediated syncope.
2003 Sep
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
Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study.
2004 Aug
Accuracy of calculated pH-dependent aqueous drug solubility.
2004 Aug
Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.
2004 Dec
Two cases of ventricular tachycardia with congenital left ventricular malformation in an adult.
2004 Feb
Antiarrhythmic drug therapy of atrial fibrillation.
2004 Feb
Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.
2004 Jan
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
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.
2004 Jul
Is this form of syncope to blame?
2004 Jun
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 21:04:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:04:56 UTC 2021
Record UNII
N6BOM1935W
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DISOPYRAMIDE PHOSPHATE
EP   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
DISOPYRAMIDE PHOSPHATE [ORANGE BOOK]
Common Name English
DISOPYRAMIDE PHOSPHATE [USAN]
Common Name English
RYTHMODAN
Brand Name English
DISOPYRAMIDE PHOSPHATE [USP MONOGRAPH]
Common Name English
DISOPYRAMIDE PHOSPHATE [EP MONOGRAPH]
Common Name English
DISOPYRAMIDE PHOSPHATE [MART.]
Common Name English
SC-7031 PHOSPHATE
Code English
DISOPYRAMIDE PHOSPHATE [VANDF]
Common Name English
DIRYTHMIN SA
Brand Name English
DISOPYRAMIDE PHOSPHATE [WHO-DD]
Common Name English
NORPACE
Brand Name English
2-PYRIDINEACETAMIDE, .ALPHA.-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-.ALPHA.-PHENYL-, (+/-)-, PHOSPHATE (1:1)
Systematic Name English
4-DIISOPROPYLAMINO-2-PHENYL-2-(2-PYRIDYL)BUTYRAMIDE PHOSPHATE
Systematic Name English
DISOPYRAMIDE PHOSPHATE [USP-RS]
Common Name English
SC-13957
Code English
DISO-DURILES
Brand Name English
NSC-756744
Code English
DISOPYRAMIDE PHOSPHATE [JAN]
Common Name English
(+/-)-.ALPHA.-(2-(DIISOPROPYLAMINO)ETHYL)-.ALPHA.-PHENYL-2-PYRIDINEACETAMIDE PHOSPHATE (1:1)
Systematic Name English
DISOPYRAMIDE PHOSPHATE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C93038
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
NCI_THESAURUS C47793
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
Code System Code Type Description
CAS
31758-86-8
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
SUPERSEDED
ECHA (EC/EINECS)
244-756-1
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
CAS
24643-91-2
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
SUPERSEDED
USP_CATALOG
1222501
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY USP-RS
RXCUI
203178
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY RxNorm
PUBCHEM
30928
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
DRUG BANK
DBSALT000899
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
CAS
22059-60-5
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL517
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
CAS
79190-73-1
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
SUPERSEDED
MERCK INDEX
M4672
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY Merck Index
FDA UNII
N6BOM1935W
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
EVMPD
SUB13637MIG
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
NCI_THESAURUS
C47497
Created by admin on Fri Jun 25 21:04:56 UTC 2021 , Edited by admin on Fri Jun 25 21:04:56 UTC 2021
PRIMARY
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