Propafenone HCl (formerly SA-79; SA79; Rytmonorm; Pronon; Arythmol; Baxarytmon; Cuxafenon; Fenoprain), the hydrochloride salt of Propafenone, is an approved class 1C anti-arrhythmic drug. It acts as a sodium channel protein inhibitor, which has been used to treat illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias.

Physicochemical Properties

Molecular Formula	C21H27NO3.HCL
Molecular Weight	377.9
Exact Mass	377.175
CAS #	34183-22-7
Related CAS #	(S)-Propafenone;107381-32-8;Propafenone;54063-53-5;Propafenone-d7 hydrochloride;1219799-06-0;Propafenone-d5 hydrochloride;1346605-05-7;Propafenone-d5 Ethyl hydrochloride;1398066-02-8;Propafenone-(phenyl-dd5) (hydrochloride);93909-48-9
PubChem CID	36708
Appearance	White to off-white solid powder
Boiling Point	519.6ºC at 760 mmHg
Melting Point	165-1670C
Flash Point	268ºC
LogP	4.434
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	11
Heavy Atom Count	26
Complexity	368
Defined Atom Stereocenter Count	0
InChi Key	XWIHRGFIPXWGEF-UHFFFAOYSA-N
InChi Code	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
Chemical Name	1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylpropan-1-one;hydrochloride
Synonyms	Propafenone HCl; Rytmonorm; Pronon; Arythmol; Baxarytmon; Cuxafenon; Fenoprain;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Voltage-gated sodium channels[1] - Rapidly activating delayed rectifier K+ current (IKr)[1] - L-type calcium channels [1]
ln Vitro	In isolated cardiac myocytes (human, canine, rabbit), Propafenone HCl (SA-79) potently blocks voltage-gated sodium channels in a use- and voltage-dependent manner. It suppresses the fast inward sodium current (INa), reducing the maximum rate of depolarization (Vmax) of cardiac action potentials. At therapeutic concentrations (0.5-2 μM), it prolongs the action potential duration (APD) by weakly blocking IKr and L-type calcium channels. Additionally, the drug inhibits abnormal automaticity and reentrant conduction in hyperexcitable cardiac cells[1]
ln Vivo	A traditional antiarrhythmic medication called propafenone (SA-79) hydrochloride is used to treat diseases like atrial and ventricular arrhythmias, which are characterized by fast heartbeats. Based on a revised classification system for rhinitis, the Allergic Rhinitis Affecting (ARIA) management guidelines prescribe intranasal antihistamines for the first-line care of intermittent intermittent, moderate/severe intermittent, and intermittent persistent rhinitis. Reduced cell excitability is the outcome of propafenone hydrochloride's disruption of sodium ion influx into cardiomyocytes. In comparison to Class Ia or Ib, propafenone hydrochloride is more selective for cells and has a higher rate, but it also blocks normal cells more thoroughly. Propafenone hydrochloride's additional action as a beta-preteraergic blocker, which results in bradycardia and arrest spasm, makes it an obvious classic Class Ic antiarrhythmic medication [1]. In canine models of experimentally induced atrial fibrillation (AF) and ventricular tachycardia (VT), intravenous administration of Propafenone HCl (SA-79) (1-2 mg/kg) converts AF to sinus rhythm in 60-80% of cases and suppresses VT episodes. Oral administration (10-20 mg/kg, twice daily) maintains sinus rhythm and reduces the frequency of recurrent arrhythmias. In rabbit models of atrioventricular nodal reentrant tachycardia (AVNRT), the drug prolongs the effective refractory period of the atrioventricular node, terminating reentrant circuits[1]
Cell Assay	Cardiac myocyte electrophysiology assay: Cardiac myocytes were isolated from adult hearts via enzymatic dissociation and plated on glass coverslips. Propafenone HCl (SA-79) was added to the extracellular recording solution at concentrations of 0.1-5 μM. Whole-cell patch-clamp recordings were performed to measure INa, IKr, and L-type calcium current (ICa,L). Voltage protocols included depolarizing steps to activate specific currents, and peak current amplitudes and kinetics were analyzed to evaluate blocking effects[1] - Action potential recording assay: Isolated cardiac myocytes were superfused with physiological saline containing Propafenone HCl (SA-79) (0.5-2 μM). Action potentials were recorded using intracellular microelectrodes or patch-clamp techniques, and parameters such as Vmax, APD50, and APD90 were quantified[1]
Animal Protocol	Atrial fibrillation/ventricular tachycardia dog model: Adult mongrel dogs (15-25 kg) were anesthetized, and electrodes were implanted to induce AF/VT via electrical stimulation. Propafenone HCl (SA-79) was administered intravenously as a bolus (1-2 mg/kg) followed by a continuous infusion (0.05-0.1 mg/kg/min) if needed. Cardiac rhythm was monitored via electrocardiography for 2 hours to assess arrhythmia conversion[1] - Oral maintenance animal model: Rats (200-250 g) were administered Propafenone HCl (SA-79) dissolved in drinking water or as a gavage formulation (10-20 mg/kg, twice daily) for 2 weeks. Arrhythmias were induced weekly via electrical stimulation, and the drug's efficacy in suppressing arrhythmias was evaluated by comparing pre- and post-treatment arrhythmia incidence[1]
ADME/Pharmacokinetics	Absorption: Oral absorption of Propafenone HCl (SA-79) is rapid and nearly complete (95%), but oral bioavailability is low (3-40%) due to extensive first-pass metabolism in the liver[1] - Distribution: The drug has a large volume of distribution (2-3 L/kg) and is widely distributed in cardiac tissue, liver, and lungs[1] - Metabolism: Metabolized primarily in the liver by cytochrome P450 2D6 (CYP2D6), with minor contributions from CYP1A2 and CYP3A4. Poor metabolizers (CYP2D6 polymorphisms) have significantly higher plasma concentrations[1] - Excretion: Approximately 10% of the parent drug and 90% of metabolites are excreted in urine; a small portion is excreted in feces[1] - Half-life: Elimination half-life ranges from 2 to 10 hours, with longer half-lives in poor metabolizers (up to 17 hours)[1]
Toxicity/Toxicokinetics	Plasma protein binding: Propafenone HCl (SA-79) is highly bound to plasma proteins (95-97%), primarily to albumin[1] - Cardiovascular toxicity: High doses or overdose may cause QT interval prolongation, torsades de pointes (TdP), bradycardia, and hypotension. Risk is increased in patients with heart failure or electrolyte imbalances[1] - Non-cardiovascular toxicity: Common side effects include gastrointestinal symptoms (nausea, vomiting, constipation), central nervous system effects (dizziness, blurred vision, tremors), and skin rashes (rare)[1] - Liver/kidney toxicity: Rare cases of hepatocellular injury or renal impairment have been reported, typically reversible upon drug discontinuation[1] - Drug-drug interactions: Concomitant use with β-adrenergic blockers, digoxin, or other antiarrhythmics increases the risk of bradycardia and hypotension. Inhibitors of CYP2D6 (e.g., fluoxetine, paroxetine) increase plasma propafenone concentrations[1]
References	[1]. http://en.wikipedia.org/wiki/Propafenone.
Additional Infomation	Propafenone hydrochloride is a hydrochloride that is the monohydrochloride salt of propafenone. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used in the management of supraventricular and ventricular arrhythmias. It has a role as an anti-arrhythmia drug. It contains a propafenone(1+). Propafenone Hydrochloride is the hydrochloride salt form of propafenone with class 1C antiarrhythmic effects. Propafenone hydrochloride stabilizes the neuronal membrane by binding to and inhibiting voltage-gated sodium channels, thereby reducing sodium influx required for the initiation and conduction of impulses in Purkinje and myocardial cells. This agent produces a marked depression of phase 0 and prolonged effective refractory period in the atrio-ventricular nodal and His-Purkinje tissue, resulting in a profound decrease in excitability, conduction velocity and automaticity, thereby counteracting atrial and ventricular arrythmias. An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. See also: Propafenone (has active moiety). Propafenone HCl (SA-79) is a class Ic antiarrhythmic drug with potent sodium channel-blocking activity[1] - Clinical indications include the treatment of life-threatening ventricular arrhythmias, conversion of atrial fibrillation/flutter to sinus rhythm, and prevention of recurrent paroxysmal supraventricular tachycardia[1] - Its antiarrhythmic mechanism involves slowing cardiac conduction (via sodium channel blockade) and prolonging refractoriness, thereby terminating reentrant arrhythmias and suppressing abnormal automaticity[1] - The drug is available in oral (tablets, extended-release capsules) and intravenous formulations for acute and chronic arrhythmia management[1] - FDA-approved for use in adults; use in pediatric patients is off-label and requires careful dose adjustment[1]

Solubility Data

Solubility (In Vitro)

DMSO:69 mg/mL (182.6 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6462 mL	13.2310 mL	26.4620 mL
	5 mM	0.5292 mL	2.6462 mL	5.2924 mL
	10 mM	0.2646 mL	1.3231 mL	2.6462 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.