DISOPYRAMIDE

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 Search

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
Sources: http://www.drugbank.ca/drugs/DB00280
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: http://www.drugbank.ca/drugs/DB00280	Inhibitor 8146		52.5 µM [IC50]
Target ID: KATP channels, Mus musculus Sources: https://www.ncbi.nlm.nih.gov/pubmed/11504161	Inhibitor 8146		4.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ventricular arrhythmia 50 Sources: https://www.drugs.com/pro/disopyramide.html	Primary		Approved 8307	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

C_max

Value	Dose	Co-administered	Analyte	Population
3.08 mg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/3524956/	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

Value	Dose	Co-administered	Analyte	Population
27.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059444/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7059444/	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 REVIEW https://pubmed.ncbi.nlm.nih.gov/3524956/	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
35% REVIEW https://pubmed.ncbi.nlm.nih.gov/3524956/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/15837258	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: https://pubmed.ncbi.nlm.nih.gov/15837258	Disc. AE: Dry mouth, Prostatism... AEs leading to discontinuation/dose reduction: Dry mouth (7%) Prostatism (7%) Sources: https://pubmed.ncbi.nlm.nih.gov/15837258

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/15837258	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: https://pubmed.ncbi.nlm.nih.gov/15837258
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: https://pubmed.ncbi.nlm.nih.gov/15837258	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: https://pubmed.ncbi.nlm.nih.gov/15837258

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670			inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
K+ channels 55 Kv1.5 25 OCT transporters 13	P-gp 1491 K+ channels 2 OCT1 317 OCT2 336 CYP 252

Drug as perpetrator

Target	Modality	Activity
K+ channels 55	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/11504161/	yes [IC50 4.8 uM]
Kv1.5 40	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/18818480/	yes
OCT transporters 13	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/29247868/	yes

Drug as victim

Target	Modality	Activity
K+ channels 2	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/9550298/	likely [EC50 1.8 uM]
CYP 252	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/18027986/	likely
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	likely
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10901704/; https://pubmed.ncbi.nlm.nih.gov/15449971/	yes
OCT1 317	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes
OCT2 336	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://pubmed.ncbi.nlm.nih.gov/16842817/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4657	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4657
ChemicalBook	CB1285468	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1285468
MolPort	MolPort-003-846-985	https://www.molport.com/shop/molecule-link/MolPort-003-846-985
eMolecules	537636	https://www.emolecules.com/cgi-bin/more?vid=537636

PubMed

Title	Date	PubMed
Acquired long QT syndrome due to antiarrhythmic drugs and bradyarrhythmias.	1992 Jan 27	1562120
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.	1992 Nov	1423949
Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.	1999 Apr	10234723
Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans.	2000 Aug	10901704
Potentially fatal interaction between azithromycin and disopyramide.	2000 Sep	11025903
Comparative safety of the different macrolides.	2001	11574199
Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy.	2001 Apr	11509917
The effects of flecainide on ATP-sensitive K(+) channels in pig urethral myocytes.	2001 Jul	11429398
Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules.	2001 Nov	11758759
Enantioselective binding of disopyramide to alpha1-acid glycoprotein and its variants.	2001 Oct	11758636
Use of beta-blockers in atrial fibrillation.	2002	14727997
Strategy for the management of vasovagal syncope.	2002	12027777
Risk of mortality in a cohort of patients newly diagnosed with chronic atrial fibrillation.	2002	11897013
[Role amiodarone in sinus rhythm maintenance after successful cardioversion in patients with chronic non-valvular atrial fibrillation].	2002 Dec	12687927
MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs.	2002 Dec	12499648
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	12224826
Maintaining stability of sinus rhythm in atrial fibrillation: antiarrhythmic drugs versus ablation.	2002 Sep	12169239
Effects of orthostatic self-training on head-up tilt testing for the prevention of tilt-induced neurocardiogenic syncope: comparison of pharmacological therapy.	2003 Apr	12716081
Capillary electrophoretic study on pH dependence of enantioselective disopyramide binding to genetic variants of human alpha1-acid glycoprotein.	2003 Aug	12964601
The effect of commonly used drugs on angiogenesis.	2003 Jan-Feb	12680218
[Drug therapy of atrial fibrillation].	2003 Jun 15	12866149
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	12804730
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	14612892
[Drug binding analysis of human alpha 1-acid glycoprotein using capillary electrophoresis].	2003 Sep	14513769
Accuracy of calculated pH-dependent aqueous drug solubility.	2004 Aug	15265508
Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.	2004 Dec	14745562
Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.	2004 Jan	15028073
Pharmacological treatment of reflex syncope.	2004 Oct	15480933
Myocardial bundles with slow conduction properties are present on the left interventricular septal surface of normal human hearts.	2004 Sep	15363072
Human organic cation transporter 3 mediates the transport of antiarrhythmic drugs.	2004 Sep 19	15363950
Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring.	2005 Feb	15658999
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.	2005 Feb	15342952

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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Name

Type

Language

DISOPYRAMIDE

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