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Details

Stereochemistry RACEMIC
Molecular Formula C21H27NO3.ClH
Molecular Weight 377.905
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROPAFENONE HYDROCHLORIDE

SMILES

Cl.CCCNCC(O)COC1=CC=CC=C1C(=O)CCC2=CC=CC=C2

InChI

InChIKey=XWIHRGFIPXWGEF-UHFFFAOYSA-N
InChI=1S/C21H27NO3.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula C21H27NO3
Molecular Weight 341.444
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
7.6 nM [IC50]
5.1 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RYTHMOL
Primary
RYTHMOL

Cmax

ValueDoseCo-administeredAnalytePopulation
189.94 ng/mL
150 mg single, oral
PROPAFENONE plasma
Homo sapiens
314 ng/mL
300 mg single, oral
PROPAFENONE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
322.43 ng × h/mL
150 mg single, oral
PROPAFENONE plasma
Homo sapiens
2900 ng × h/mL
300 mg single, oral
PROPAFENONE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.61 h
300 mg single, oral
PROPAFENONE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
4.1%
PROPAFENONE plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Initiate therapy with 150 mg given every 8 hours. As needed, uptitrate in 3-4 days to 225-300 mg every 8 hours
Route of Administration: Oral
In Vitro Use Guide
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
Record UNII
33XCH0HOCD
Record Status Validated (UNII)
Record Version