Propafenone Chemical Properties

Boiling point:

519.6±50.0 °C(Predicted)

Density 

1.096±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: 68 mg/mL (199.16 mM);Ethanol: 41 mg/mL (120.08 mM)

form 

Solid

pka

pKa 9.27 (Uncertain)

color 

White to Off-White

Water Solubility 

759.9ug/L(22.5 ºC)

CAS DataBase Reference

54063-53-5(CAS DataBase Reference)

NIST Chemistry Reference

Propafenone(54063-53-5)

Safety Information

Hazard Codes 

T

Risk Statements 

46-22

Safety Statements 

53-36/37/39-45

WGK Germany 

3

RTECS 

UH2833000

Hazardous Substances Data

54063-53-5(Hazardous Substances Data)

Propafenone Usage And Synthesis

Uses

Cardiac depressant (anti-arrhythmic).

Definition

ChEBI: An aromatic ketone that is 3-(propylamino)propane-1,2-diol in which the hydrogen of the primary hydroxy group is replaced by a 2-(3-phenylpropanoyl)phenyl group. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used as the hydroch oride salt in the management of supraventricular and ventricular arrhythmias.

brand name

Rythmol (Reliant);Arythmol;Nofenan;Nofenon;Nomorytmin;Normotrytmin (r) 10 mg;Prolekofen;Retmonorm;Ryhmonorma;Rythmole;Rytmonorm.

World Health Organization (WHO)

Propafenone, a membrane-stabilizing antiarrhythmic agent, was introduced into medicine in the mid 1980s. Shortly afterwards, its use became associated with cases of severe cardiac arrhythmias, which led to notable restrictions in the drug's indications in at least two countries. See also WHO comment for flecainide.

General Description

Propafenone, 2-[2＇-hydroxy-3-(propylamino)propoxy]-3-phenylpropiophenone (Rythmol), a classIC antiarrhythmic drug, contains a chiral center and is marketedas the racemic mixture. Therapy with the racemicmixture of propafenone produces effects that can be attributedto both (S) and (R) enantiomers. Although (R) and (S)enantiomers exert similarNa⁺channel–blocking effects, the(S) enantiomer also produces aβ-adrenergic blockade. As aresult, the (S) enantiomer is reported to be 40-fold morepotent than the (R) enantiomer as an antiarrhythmic agent.The enantiomers also display stereoselective dispositioncharacteristics. The (R) enantiomer is cleared more quickly.Hepatic metabolism is polymorphic and determined genetically.Ten percent of Caucasians have a reduced capacity tohydroxylate the drug to form 5-hydroxypropafenone. Thispolymorphic metabolism accounts for the interindividualvariability in the relationships between dose and concentrationand, thus, variability in the pharmacodynamic effects ofthe drug. The 5-hydroxy metabolites of both enantiomersare as potent as the parent compound in blocking Na⁺channels.Propafenone also depresses the slow inward current ofCa2⁺ions.

Mechanism of action

Propafenone has not only pronounced class I effects but also class II (structure related) and class IV activities . Accordingly, it has a broad spectrum of activity against ventricular and supraventricular arrhythmias.

Clinical Use

Propafenone has been used for acute termination orlong-term suppression of ventricular arrhythmias. It isbound in excess of 95% to 1-acid glycoprotein in theplasma. It is absorbed effectively, but bioavailability is estimatedto be less than 20% because of first-pass metabolism.Less than 1% is eliminated as unchanged drug. Therapywith propafenone may produce effects that can be attributedto both (S) and (R) enantiomers. Thus, the effects may bemodulated because of an enantiomer–enantiomer interactionwhen patients are treated with the racemate.

Side effects

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone.
As with other members of class IC, propafenone may interact in an unfavorable way with other agents that depress A-V nodal function, intraventricular conduction, or myocardial contractility. Overall, 21 to 32% of patients have adverse effects. The most common are dizziness or light-headedness, metallic taste, nausea, and vomiting; the most serious are proarrhythmic events.

Precautions

Propafenone is contraindicated in the presence of severe or uncontrolled congestive heart failure; cardiogenic shock; sinoatrial, A-V, and intraventricular disorders of conduction; and sinus node dysfunction, such as sick sinus syndrome. Other contraindications include severe bradycardia, hypotension, obstructive pulmonary disease, and hepatic and renal failure. Because of its weak β-blocking action, propafenone may cause possible dose-related bronchospasm.This problem is greatest in patients who are slow metabolizers.

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