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Details

Stereochemistry RACEMIC
Molecular Formula C21H27NO3
Molecular Weight 341.4448
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROPAFENONE

SMILES

CCCNCC(COc1ccccc1C(=O)CCc2ccccc2)O

InChI

InChIKey=JWHAUXFOSRPERK-UHFFFAOYSA-N
InChI=1S/C21H27NO3/c1-2-14-22-15-18(23)16-25-21-11-7-6-10-19(21)20(24)13-12-17-8-4-3-5-9-17/h3-11,18,22-23H,2,12-16H2,1H3

HIDE SMILES / InChI

Molecular Formula C21H27NO3
Molecular Weight 341.4448
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: https://www.drugbank.ca/drugs/DB01182 | http://reference.medscape.com/drug/rythmol-propafenone-342307 | https://www.drugs.com/pro/propafenone.html | https://www.ncbi.nlm.nih.gov/pubmed/26588045

Propafenone (brand name Rythmol SR or Rytmonorm) is a class 1C anti-arrhythmic medication, which treats illnesses associated with rapid heartbeats such as atrial and ventricular arrhythmias. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy. Propafenone is metabolized primarily in the liver. Because of its short half-life, it requires dosing two or three times daily to maintain steady blood levels. The long-term safety of propafenone is unknown. Because it is structurally similar to another anti-arrhythmic medicine, flecainide, similar cautions should be exercised in its use. Flecainide and propafenone, like other antiarrhythmic drugs, have been shown to increase the occurrence of arrhythmias (5.3% for propafenone, Teva physician prescribing information), primarily in patients with underlying heart disease. However, their use in structurally normal hearts is considered safe.

Originator

Sources: Journal of the American Geriatrics Society (1961), 9, 491-7.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RYTHMOL

Approved Use

Propafenone HCl Extended Release Capsules is indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: •The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone ER capsules to control ventricular rate during AF. •Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended. • The effect of propafenone on mortality has not been determined [see BOXED WARNING

Launch Date

628128000000
Primary
RYTHMOL

Approved Use

Propafenone HCl Extended Release Capsules is indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: •The use of propafenone ER capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone ER capsules to control ventricular rate during AF. •Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended. • The effect of propafenone on mortality has not been determined [see BOXED WARNING

Launch Date

628128000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
314 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
189.94 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2900 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
322.43 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.61 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4.1%
PROPAFENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Other AEs: Monocyte count increased, Eosinophil count increased...
Other AEs:
Monocyte count increased (0.7%)
Eosinophil count increased (0.7%)
Platelet count decreased (0.7%)
Cardiac failure congestive (1.5%)
Coronary artery disease NOS (0.7%)
Myocardial infarction (0.7%)
Abdominal pain NOS (0.7%)
Diarrhea NOS (0.7%)
Chest pain (1.5%)
Pneumonia NOS (0.7%)
Urinary tract infection NOS (0.7%)
Prothrombin level decreased (0.7%)
Headache (0.7%)
Syncope (0.7%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain NOS 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Coronary artery disease NOS 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Diarrhea NOS 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Eosinophil count increased 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Headache 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Monocyte count increased 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Myocardial infarction 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Platelet count decreased 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Pneumonia NOS 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Prothrombin level decreased 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Syncope 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Urinary tract infection NOS 0.7%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Cardiac failure congestive 1.5%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Chest pain 1.5%
425 mg 2 times / day multiple, oral
Highest studied dose
Dose: 425 mg, 2 times / day
Route: oral
Route: multiple
Dose: 425 mg, 2 times / day
Sources:
unhealthy, adult
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
yes
yes
yes (co-administration study)
Comment: amiodarone and tobacco (CYP1A2 inhibitor) can be expected to cause increased plasma levels of propafenone
yes
yes (co-administration study)
Comment: ketoconazole, erythromycin, saquinavir, and grapefruit juice for (CYP3A4 inhibitors) can be expected to cause increased plasma levels of propafenone; The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 sinhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse event
yes
yes (pharmacogenomic study)
Comment: Multiple studies have found that genetic variants in the CYP2D6 gene influence the plasma drug levels of propafenone
Tox targets
PubMed

PubMed

TitleDatePubMed
An organic psychosis due to a venlafaxine-propafenone interaction.
2001
Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long term outcome after right atrial isthmus ablation.
2001 Apr
[Clinical and experimental study of effect of yangxin fumai oral liquid in treating patients with extrasystole].
2001 Feb
The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment.
2001 Jul
Late-breaking clinical trials at the American Heart Association's scientific sessions 2001.
2001 Nov 20
Transient outward current inhibition by propafenone and 5-hydroxypropafenone in cultured neonatal rat ventricular myocytes.
2001 Sep
Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.
2001 Sep-Oct
[Pharmacological cardioversion of atrial fibrillation with intravenous and oral propafenone].
2002
Impact of stereoselectivity on the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.
2002
Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment.
2002
Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
2002 Aug 7
Evidence for the possible involvement of Ca2+ entry blockade in the relaxation by class I antiarrhythmic drugs in the isolated pig coronary smooth muscle.
2002 Jan
New use of antiarrhythmia drugs in Saskatchewan.
2002 Jan
Propafenone-related cholestatic hepatitis in an elderly patient.
2002 Jul
[Efficacy and tolerance of propafenone after correction of atrial fibrillation: PEPS pharmaco-epidemiologic study].
2002 Jun
Similarity based SAR (SIBAR) as tool for early ADME profiling.
2002 Nov
Human variability in polymorphic CYP2D6 metabolism: is the kinetic default uncertainty factor adequate?
2002 Nov
Lopinavir/ritonavir: a review of its use in the management of HIV infection.
2003
High-throughput screening to estimate single or multiple enzymes involved in drug metabolism: microtitre plate assay using a combination of recombinant CYP2D6 and human liver microsomes.
2003 Aug
Propafenone hepatotoxicity: report of two new cases.
2003 Feb
Class I or class III agents for atrial fibrillation: are asking the right question?
2003 Jul
A novel two-pore domain K+ channel, TRESK, is localized in the spinal cord.
2003 Jul 25
[Drug therapy of atrial fibrillation].
2003 Jun 15
Effects of a series of dihydroanthracene derivatives on drug efflux in multidrug resistant cancer cells.
2003 Mar
Left atrial size after cardioversion for atrial fibrillation: effect of external direct current shock.
2003 Mar
Molecular site of action of the antiarrhythmic drug propafenone at the voltage-operated potassium channel Kv2.1.
2003 Mar
Patents

Sample Use Guides

Initiate therapy with 150 mg given every 8 hours.
Route of Administration: Oral
Hela cells were used for activity evaluation. Proliferation percentage was determined by the SRB assay. Cells were incubated with the Propafenone at the concentrations of 0.005-0.2 g/L for 48 h, and the cell proliferation/viability was determined using the survival percentage with the cells treated only with dimethyl sulfoxide (DMSO) at 0.1% as a reference
Substance Class Chemical
Created
by admin
on Sat Jun 26 10:02:48 UTC 2021
Edited
by admin
on Sat Jun 26 10:02:48 UTC 2021
Record UNII
68IQX3T69U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PROPAFENONE
INCI   INN   MI   VANDF   WHO-DD  
INN   INCI  
Official Name English
PROPAFENONE [MI]
Common Name English
PROPAFENON HEXAL
Brand Name English
PROPAFENONE [INCI]
Common Name English
PROPAFENONE [VANDF]
Common Name English
PROPAFENONE [WHO-DD]
Common Name English
PROPAFENONE [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
LIVERTOX 806
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
NDF-RT N0000175426
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
NCI_THESAURUS C47793
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
WHO-VATC QC01BC03
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
WHO-ATC C01BC03
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
Code System Code Type Description
EPA CompTox
54063-53-5
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
DRUG BANK
DB01182
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
IUPHAR
2561
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
DRUG CENTRAL
2291
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
ECHA (EC/EINECS)
258-955-6
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
WIKIPEDIA
PROPAFENONE
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL631
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
FDA UNII
68IQX3T69U
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
LACTMED
Propafenone
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
PUBCHEM
4932
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
RXCUI
8754
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY RxNorm
CAS
54063-53-5
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
HSDB
7929
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
INN
3312
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
MERCK INDEX
M9178
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY Merck Index
MESH
D011405
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
NCI_THESAURUS
C61909
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
EVMPD
SUB10094MIG
Created by admin on Sat Jun 26 10:02:48 UTC 2021 , Edited by admin on Sat Jun 26 10:02:48 UTC 2021
PRIMARY
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC
Elimination
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC Population
PHARMACOKINETIC