DISOPYRAMIDE PHOSPHATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H29N3O.H3O4P
Molecular Weight	437.4696
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	C21H29N3O
Molecular Weight	339.4745
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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

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 8297		52.5 µM [IC50]
KATP channels, Mus musculus 2 Target ID: KATP channels, Mus musculus Sources: https://www.ncbi.nlm.nih.gov/pubmed/11504161	Inhibitor 8297		4.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ventricular arrhythmia 50 Sources: https://www.drugs.com/pro/disopyramide.html	Primary		Approved 8429	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 1985

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 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
K+ channels 70 Kv1.5 26 OCT transporters 14	P-gp 1537 K+ channels 2 OCT1 327 OCT2 355 CYP 270

Drug as perpetrator

Target	Modality	Activity
K+ channels 70	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11504161/	yes [IC50 4.8 uM]
Kv1.5 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18818480/	yes
OCT transporters 14	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29247868/	yes

Drug as victim

Target	Modality	Activity
K+ channels 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9550298/	likely [EC50 1.8 uM]
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18027986/	likely
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	likely
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10901704/; https://pubmed.ncbi.nlm.nih.gov/15449971/	yes
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12440152/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
Use of beta-blockers in atrial fibrillation.	2002	14727997
[Role amiodarone in sinus rhythm maintenance after successful cardioversion in patients with chronic non-valvular atrial fibrillation].	2002 Dec	12687927
[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
Ropivacaine combined with various anti-arrhythmic drugs results in mild alterations in myocardial contractility in pigs.	2003 Dec	14656782
Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants.	2003 Dec	14616427
Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.	2003 Dec 16	14678922
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	14678921
Hypertrophic obstructive cardiomyopathy: mechanism of obstruction and response to therapy.	2003 Fall	14668688
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
[An approach to complete the manual for determination of serum pirmenol levels].	2003 Nov	14631760
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
QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs.	2003 Nov-Dec	14624285
[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
[Drug binding analysis of human alpha 1-acid glycoprotein using capillary electrophoresis].	2003 Sep	14513769
Randomized clinical trials of neurally mediated syncope.	2003 Sep	12950522
Interactions between grapefruit juice and cardiovascular drugs.	2004	15449971
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
Accuracy of calculated pH-dependent aqueous drug solubility.	2004 Aug	15265508
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
Antiarrhythmic drug therapy of atrial fibrillation.	2004 Feb	14994845
Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships.	2004 Jan	15028073
Theoretical possibilities for the development of novel antiarrhythmic drugs.	2004 Jan	14754422
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
Is this form of syncope to blame?	2004 Jun	15317281
Effects of antiarrhythmic agents on left ventricular function during exercise in patients with chronic left ventricular dysfunction.	2004 May	15233282
Failure of disopyramide to improve right ventricular outflow tract obstruction after living-donor lobar lung transplantation.	2004 Nov	15502393
Pharmacological treatment of reflex syncope.	2004 Oct	15480933
Acute ventricular rate control in atrial fibrillation and atrial flutter.	2004 Oct	15336799
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
Toxic interactions between fluconazole and disopyramide in chick embryos.	2005 Jan	15635181
Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone.	2005 Jan	15606453

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 15 17:41:32 GMT 2023` Edited by `admin` on `Fri Dec 15 17:41:32 GMT 2023`
Record UNII	N6BOM1935W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DISOPYRAMIDE PHOSPHATE

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 [WHO-DD]

Common Name

English

DISOPYRAMIDE PHOSPHATE [VANDF]

Common Name

English

DIRYTHMIN SA

Brand 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