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 8228		52.5 µM [IC50]
Target ID: KATP channels, Mus musculus Sources: https://www.ncbi.nlm.nih.gov/pubmed/11504161	Inhibitor 8228		4.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ventricular arrhythmia 50 Sources: https://www.drugs.com/pro/disopyramide.html	Primary		Approved 8360	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 1709			inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
K+ channels 56 Kv1.5 26 OCT transporters 13	P-gp 1527 K+ channels 2 OCT1 322 OCT2 348 CYP 266

Drug as perpetrator

Target	Modality	Activity
K+ channels 56	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11504161/	yes [IC50 4.8 uM]
Kv1.5 41	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18818480/	yes
OCT transporters 13	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29247868/	yes

Drug as victim

Target	Modality	Activity
K+ channels 2	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9550298/	likely [EC50 1.8 uM]
CYP 266	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/18027986/	likely
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	likely
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10901704/; https://pubmed.ncbi.nlm.nih.gov/15449971/	yes
OCT1 322	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes
OCT2 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 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
[Torsades de pointes ventricular tachycardia induced by disopyramide at therapeutic serum concentration].	1992 Aug 20	1412257
Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.	1992 Nov	1423949
Population pharmacokinetics, protein binding and antiarrhythmic effects of disopyramide enantiomers in arrhythmic patients.	2001	12067143
[Acute intoxication with disopyramide: case report with literature review].	2001 Nov-Dec	11878114
Disopyramide: interactions with marcolide antibiotics.	2001 Oct	11824433
Impact of stereoselectivity on the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.	2002	12102640
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
Cisapride reverses the anticholinergic effect of disopyramide on the isolated guinea-pig urinary bladder.	2002 Apr	12000530
[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
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	12483455
Disopyramide-induced neuropathy.	2002 Feb 26	11865156
Effective disopyramide treatment in a boy with mid-ventricular hypertrophic obstructive cardiomyopathy.	2002 Jul	12135145
Quantification of pilsicainide in serum by capillary electrophoresis.	2002 Jul 20	12093491
[Antiarrhythmic drugs in atrial fibrillation].	2002 Jun 15	12187895
What is the minimal pacing rate that prevents torsades de pointes? Insights from patients with permanent pacemakers.	2002 Nov	12494620
[Molecular diversity of organic cation transporter (OCT) mediating renal excretion of drugs].	2002 Nov	12440152
Atrial fibrillation threshold predicted long-term efficacy of pharmacological treatment of patients without structural heart disease.	2002 Oct	12408258
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	12379159
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
[Anti-arrhythmic therapy: diagnostic possibilities of signal-averaged electrocardiography and heart rate variability].	2003	12891276
[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	12728540
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
Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.	2003 Aug 18	12873512
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	12527670
The effect of commonly used drugs on angiogenesis.	2003 Jan-Feb	12680218
Inhibitory effect of erythromycin on potassium currents in rat ventricular myocytes in comparison with disopyramide.	2003 Jul	12906757
Interaction of quinidine, disopyramide and metoprolol with melanin in vitro in relation to drug-induced ocular toxicity.	2003 Jul	12889538
Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage.	2003 Jun	12793884
[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
Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamide.	2003 Jun 27	12804575
Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes.	2003 Mar	12652328
[Relationship between duration of arrhythmia and subsequent preventive effect of disopyramide after cardioversion in patients with symptomatic paroxysmal and persistent atrial fibrillation].	2003 Sep	14526660
Randomized clinical trials of neurally mediated syncope.	2003 Sep	12950522
Atrial fibrillation: rate control often better than rhythm control.	2004 Apr	15148984
Recurrent syncopic episodes as a consequence of combined Brugada syndrome and paroxysmal atrial fibrillation. Which is the therapy of choice?	2004 Apr	15094000
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	15302734
Simultaneous supraventricular tachycardias in both fetuses of a twin gestation.	2004 Dec	14745562
Two cases of ventricular tachycardia with congenital left ventricular malformation in an adult.	2004 Feb	15008699
Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.	2004 Jan	15028073
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	14685755
Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.	2004 Jul	15272206
Effects of antiarrhythmic agents on left ventricular function during exercise in patients with chronic left ventricular dysfunction.	2004 May	15233282
Pharmacological treatment of reflex syncope.	2004 Oct	15480933
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 `Thu Jul 06 00:59:38 UTC 2023` Edited by `admin` on `Thu Jul 06 00:59:38 UTC 2023`
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

α-[2-(Diisopropylamino)ethyl]-α-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