Identification

Name
Propafenone
Accession Number
DB01182  (APRD00261)
Type
Small Molecule
Groups
Approved
Description

An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated.

Structure
Thumb
Synonyms
  • 1-(2-(2-hydroxy-3-(propylamino)propoxy)phenyl)-3-phenyl-1-propanone
  • 2-(2'-hydroxy-3'-propylaminopropoxy)-ω-phenylpropiophenone
  • Propafenona
  • Propafenonum
Product Ingredients
IngredientUNIICASInChI Key
Propafenone hydrochloride33XCH0HOCD34183-22-7XWIHRGFIPXWGEF-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PropafenoneTablet300 mgOralSanis Health Inc2010-02-16Not applicableCanada
PropafenoneTablet150 mgOralSanis Health Inc2010-02-16Not applicableCanada
Propafenone HClTablet, film coated225 mg/1OralETHEX2007-03-28Not applicableUs
Propafenone HClTablet, film coated150 mg/1OralETHEX2007-03-28Not applicableUs
Propafenone HClTablet, film coated300 mg/1OralETHEX2007-03-28Not applicableUs
Propafenone hydrochlorideTablet, film coated225 mg/1OralVintage Pharmaceuticals, LLC2006-10-302006-10-30Us
Propafenone hydrochlorideTablet, film coated150 mg/1OralVintage Pharmaceuticals, LLC2006-10-302006-10-30Us
Propafenone hydrochlorideTablet, film coated300 mg/1OralVintage Pharmaceuticals, LLC2006-10-302006-10-30Us
Propafenone-150Tablet150 mgOralPro Doc Limitee2008-03-072016-07-18Canada
Propafenone-300Tablet300 mgOralPro Doc Limitee2009-05-262016-07-18Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-propafenoneTablet150 mgOralApotex Corporation2001-02-22Not applicableCanada
Apo-propafenoneTablet300 mgOralApotex Corporation2001-02-22Not applicableCanada
Myl-propafenoneTablet300 mgOralMylan Pharmaceuticals2002-03-08Not applicableCanada
Myl-propafenoneTablet150 mgOralMylan Pharmaceuticals2002-03-08Not applicableCanada
Mylan-propafenoneTablet300 mgOralMylan Pharmaceuticals2017-10-31Not applicableCanada
Mylan-propafenoneTablet150 mgOralMylan Pharmaceuticals2017-10-31Not applicableCanada
Nu-propafenoneTablet150 mgOralNu Pharm IncNot applicableNot applicableCanada
PMS-propafenoneTablet150 mgOralPharmascience Inc2001-04-092017-05-24Canada
PMS-propafenoneTablet150 mgOralPharmascience IncNot applicableNot applicableCanada
PMS-propafenoneTablet300 mgOralPharmascience Inc2008-02-22Not applicableCanada
Categories
UNII
68IQX3T69U
CAS number
54063-53-5
Weight
Average: 341.444
Monoisotopic: 341.199093735
Chemical Formula
C21H27NO3
InChI Key
JWHAUXFOSRPERK-UHFFFAOYSA-N
InChI
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
IUPAC Name
1-{2-[2-hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylpropan-1-one
SMILES
CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC1=CC=CC=C1

Pharmacology

Indication

Used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. Also used for the treatment of life-threatening documented ventricular arrhythmias, such as sustained ventricular tachycardia.

Associated Conditions
Pharmacodynamics

Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It works by slowing the influx of sodium ions into the cardiac muscle cells, causing a decrease in excitablity of the cells. Propafenone has local anesthetic activity approximately equal to procaine.

Mechanism of action

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.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Human
APotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UBeta-1 adrenergic receptor
antagonist
Human
UBeta-2 adrenergic receptor
antagonist
Human
Absorption

Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).

Volume of distribution
  • 252 L
Protein binding

97%

Metabolism

Metabolized primarily in the liver where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxypropafenone and N-depropylpropafenone. These metabolites have antiarrhythmic activity comparable to propafenone but are present in concentrations less than 25% of propafenone concentrations.

Route of elimination

Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets.

Half life

2-10 hours

Clearance
Not Available
Toxicity

Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*9Not Available2615-2617delAAGADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*10Not Available100C>T / 1661G>C  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*14BNot Available1758G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*17Not Available1023C>T / 2850C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*18Not Available4133dupGTGCCCACTADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*29Not Available1659G>A / 1661G>C  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*41Not Available2988G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*49Not Available100C>T / -1426C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*50Not Available1720A>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*54Not Available100C>T / 1039C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*55Not Available1661G>C / 2850C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*59Not Available1661G>C / 2291G>A  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 2D6CYP2D6*72Not Available-1426C>T / -1235A>G  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*20Not Available1461_1462insAADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*26Not Available802C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*8Not Available13908G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*11Not Available1088C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*12Not Available1117C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*13Not Available1247C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*16ANot Available554C>GADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*16BNot Available554C>GADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 3A4CYP3A4*17Not Available566T>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*6Not Available5090C>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*1CNot Available-3860G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*1KNot Available-739T>G / -729C>T  … show all ADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*3Not Available2116G>A / 5347T>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*4Not Available2499A>TADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*7Not Available3533G>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*8Not Available5166G>A / 5347T>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*11Not Available558C>AADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*15Not Available125C>G / 5347T>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details
Cytochrome P450 1A2CYP1A2*16Not Available2473G>A / 5347T>CADR InferredPoor drug metabolizer, increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Propafenone.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Propafenone.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Propafenone.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Propafenone.
4-hydroxycoumarinThe serum concentration of 4-hydroxycoumarin can be increased when it is combined with Propafenone.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Propafenone.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Propafenone.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Propafenone.
7,9-DimethylguanineThe serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Propafenone.
8-azaguanineThe serum concentration of 8-azaguanine can be increased when it is combined with Propafenone.
Food Interactions
  • Always take at the same time in regard to meals.
  • Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.

References

Synthesis Reference

Helmut Lietz, "Preparation of propafenone." U.S. Patent US4474986, issued May, 1974.

US4474986
General References
Not Available
External Links
Human Metabolome Database
HMDB0015313
KEGG Drug
D08435
KEGG Compound
C07381
PubChem Compound
4932
PubChem Substance
46504529
ChemSpider
4763
BindingDB
50067133
ChEBI
63619
ChEMBL
CHEMBL631
Therapeutic Targets Database
DAP000497
PharmGKB
PA451131
IUPHAR
2561
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Propafenone
ATC Codes
C01BC03 — Propafenone
AHFS Codes
  • 24:04.04.12 — Class IC Antiarrythmics
FDA label
Download (91.1 KB)
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCardiac Dysrhythmia1
1, 2RecruitingTreatmentNeoplasms1
2CompletedTreatmentFailed First Radiofrequency Ablation Procedure / Paroxysmal Atrial Fibrillation (PAF)1
3CompletedPreventionArrythmias / Cardiovascular Disease (CVD) / Heart Arrest / Heart Diseases / Myocardial Infarction / Severe ventricular arrhythmias1
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentParoxysmal Atrial Fibrillation (PAF)1
3SuspendedTreatmentNonvalvular Atrial Fibrillation1
3TerminatedTreatmentHeart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
4Not Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
4RecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableActive Not RecruitingTreatmentNonvalvular Atrial Fibrillation / Quality of Life1
Not AvailableCompletedTreatmentNonvalvular Atrial Fibrillation3
Not AvailableNot Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableRecruitingTreatmentHeart Failure, Unspecified / Recurrent Atrial Fibrillation1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableRecruitingTreatmentPersistent Atrial Fibrillation1
Not AvailableRecruitingTreatmentPremature Ventricular Complex1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • BASF Corp.
  • Cardinal Health
  • Ethex Corp.
  • GlaxoSmithKline Inc.
  • Heartland Repack Services LLC
  • KV Pharmaceutical Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Neuman Distributors Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Qualitest
  • Reliant Pharmaceuticals
  • Resource Optimization and Innovation LLC
  • UDL Laboratories
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral150 mg
TabletOral300 mg
Capsule, extended releaseOral225 1/1
Tablet, coatedOral150 mg/1
Tablet, coatedOral225 mg/1
Tablet, coatedOral300 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral225 mg/1
Tablet, film coatedOral300 mg/1
TabletOral150 mg/1
TabletOral225 mg/1
TabletOral300 mg/1
Capsule, extended releaseOral225 mg/1
Capsule, extended releaseOral325 mg/1
Capsule, extended releaseOral425 mg/1
Prices
Unit descriptionCostUnit
Rythmol SR 325 mg 12 Hour Capsule8.9USD capsule
Rythmol SR 425 mg 12 Hour Capsule8.9USD capsule
Rythmol sr 325 mg capsule8.56USD capsule
Rythmol sr 425 mg capsule8.56USD capsule
Rythmol SR 225 mg 12 Hour Capsule7.02USD capsule
Rythmol sr 225 mg capsule6.75USD capsule
Rythmol 225 mg tablet6.2USD tablet
Rythmol 300 mg tablet5.05USD tablet
Rythmol 150 mg tablet3.95USD tablet
Propafenone hcl 300 mg tablet3.03USD tablet
Propafenone hcl 225 mg tablet2.38USD tablet
Rythmol 300 mg Tablet2.09USD tablet
Propafenone hcl 150 mg tablet1.64USD tablet
Rythmol 150 mg Tablet1.18USD tablet
Apo-Propafenone 300 mg Tablet0.79USD tablet
Pms-Propafenone 300 mg Tablet0.79USD tablet
Apo-Propafenone 150 mg Tablet0.45USD tablet
Pms-Propafenone 150 mg Tablet0.45USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5681588No1994-10-282014-10-28Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleNot Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00758 mg/mLALOGPS
logP3.1ALOGPS
logP3.54ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.63ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity100.21 m3·mol-1ChemAxon
Polarizability39.75 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.996
Blood Brain Barrier-0.958
Caco-2 permeable-0.5433
P-glycoprotein substrateSubstrate0.8548
P-glycoprotein inhibitor IInhibitor0.8565
P-glycoprotein inhibitor IIInhibitor0.874
Renal organic cation transporterNon-inhibitor0.7204
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.5499
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.7066
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8931
Ames testNon AMES toxic0.8446
CarcinogenicityNon-carcinogens0.8879
BiodegradationNot ready biodegradable0.803
Rat acute toxicity2.3795 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5383
hERG inhibition (predictor II)Inhibitor0.8915
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as linear 1,3-diarylpropanoids. These are organic compounds with a structure based on a C6-C3-C6 skeleton, where the two benzene rings are not linked together.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Linear 1,3-diarylpropanoids
Sub Class
Not Available
Direct Parent
Linear 1,3-diarylpropanoids
Alternative Parents
Alkyl-phenylketones / Butyrophenones / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Aryl alkyl ketones / Alkyl aryl ethers / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines
show 3 more
Substituents
Linear 1,3-diarylpropanoid / Alkyl-phenylketone / Butyrophenone / Phenylketone / Benzoyl / Phenol ether / Phenoxy compound / Aryl ketone / Aryl alkyl ketone / Alkyl aryl ether
show 18 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
secondary alcohol, secondary amino compound, aromatic ketone (CHEBI:63619)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Mergenthaler J, Haverkamp W, Huttenhofer A, Skryabin BV, Musshoff U, Borggrefe M, Speckmann EJ, Breithardt G, Madeja M: Blocking effects of the antiarrhythmic drug propafenone on the HERG potassium channel. Naunyn Schmiedebergs Arch Pharmacol. 2001 Apr;363(4):472-80. [PubMed:11330342]
  2. Arias C, Gonzalez T, Moreno I, Caballero R, Delpon E, Tamargo J, Valenzuela C: Effects of propafenone and its main metabolite, 5-hydroxypropafenone, on HERG channels. Cardiovasc Res. 2003 Mar;57(3):660-9. [PubMed:12618228]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. McLeod AA, Stiles GL, Shand DG: Demonstration of beta adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylate cyclase activation studies. J Pharmacol Exp Ther. 1984 Feb;228(2):461-6. [PubMed:6141285]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. McLeod AA, Stiles GL, Shand DG: Demonstration of beta adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylate cyclase activation studies. J Pharmacol Exp Ther. 1984 Feb;228(2):461-6. [PubMed:6141285]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK: Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol. 1993 Jan;43(1):120-6. [PubMed:8423765]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK: Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol. 1993 Jan;43(1):120-6. [PubMed:8423765]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Kobayashi K, Nakajima M, Chiba K, Yamamoto T, Tani M, Ishizaki T, Kuroiwa Y: Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2. Br J Clin Pharmacol. 1998 Apr;45(4):361-8. [PubMed:9578183]
  4. Michaud V, Mouksassi MS, Labbe L, Belanger PM, Ferron LA, Gilbert M, Grech-Belanger O, Turgeon J: Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans. Ther Drug Monit. 2006 Dec;28(6):779-83. doi: 10.1097/01.ftd.0000249945.64978.33. [PubMed:17164694]
  5. Labbe L, O'Hara G, Lefebvre M, Lessard E, Gilbert M, Adedoyin A, Champagne J, Hamelin B, Turgeon J: Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther. 2000 Jul;68(1):44-57. doi: 10.1067/mcp.2000.108023. [PubMed:10945315]
  6. Propafenone FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schmid D, Ecker G, Kopp S, Hitzler M, Chiba P: Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements. Biochem Pharmacol. 1999 Nov 1;58(9):1447-56. [PubMed:10513988]
  2. Bachmakov I, Rekersbrink S, Hofmann U, Eichelbaum M, Fromm MF: Characterisation of (R/S)-propafenone and its metabolites as substrates and inhibitors of P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2005 Mar;371(3):195-201. Epub 2005 Apr 15. [PubMed:15900513]
  3. Singh P, Paul K: Studies of interactions between uracil-based hybrid molecules and P-glycoprotein--search for multidrug resistance modulators. Bioorg Med Chem. 2006 Nov 1;14(21):7183-6. Epub 2006 Jul 14. [PubMed:16843673]
  4. Woodland C, Verjee Z, Giesbrecht E, Koren G, Ito S: The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther. 1997 Oct;283(1):39-45. [PubMed:9336306]
  5. Tmej C, Chiba P, Huber M, Richter E, Hitzler M, Schaper KJ, Ecker G: A combined Hansch/Free-Wilson approach as predictive tool in QSAR studies on propafenone-type modulators of multidrug resistance. Arch Pharm (Weinheim). 1998 Jul-Aug;331(7-8):233-40. [PubMed:9747179]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:35