 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C21H27NO3 |
| Molecular Weight | 341.45 |
| Exact Mass | 341.199 |
| CAS # | 54063-53-5 |
| Related CAS # | Propafenone hydrochloride;34183-22-7;(S)-Propafenone;107381-32-8;Propafenone-d7 hydrochloride;1219799-06-0;Propafenone-d5 hydrochloride;1346605-05-7 |
| PubChem CID | 4932 |
| Appearance | White to off-white solid powder |
| Density | 1.096 g/cm3 |
| Melting Point | 171 - 174ºC |
| Flash Point | 268ºC |
| Index of Refraction | 1.557 |
| LogP | 3.632 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 25 |
| Complexity | 368 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | JWHAUXFOSRPERK-UHFFFAOYSA-N |
| InChi Code | 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 |
| Chemical Name | 1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylpropan-1-one |
| 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 |
| 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 |
Beta-adrenergic receptors (β2-adrenoceptors, IC50 = 32 ± 19 nmol/L for displacement of 125I-iodopindolol) Sodium channels (cardiac)[1] |
| ln Vitro |
The growth of esophageal squamous cell carcinoma (ESCC) cells is inhibited by propafenone (5–25 μM) [3]. Propafenone reduces the potential of the mitochondrial membrane and decreases the expression of Bcl-xL and Bcl-2, which results in mitochondrial malfunction [3]. The anti-apoptotic proteins Bcl-xL and Bcl-2 were found to have their expression levels dramatically down-regulated in ESCC cells with propafenone (10 and 20 μ m) treatment. Additionally, propafenone can lower p-ERK expression [3]. Propafenone displaced 125I-iodopindolol from β2-adrenoceptors on human lymphocytes in a concentration-dependent manner. The displacement curve was monophasic. The IC50 value for propafenone was 32 ± 19 nmol/L (Ki = 12 ± 4 nmol/L). In comparison, its metabolite N-desalkyl propafenone had an IC50 of 90 ± 38 nmol/L (Ki = 37 ± 15 nmol/L), and 5-hydroxy propafenone had an IC50 of 478 ± 154 nmol/L (Ki = 181 ± 61 nmol/L), indicating that the parent drug propafenone has the highest affinity for β2-adrenoceptors among the three compounds.[1] In vitro studies readily demonstrate the beta-blocking actions of propafenone.[1] As a sodium-channel blocking agent, propafenone is effective in managing atrial and ventricular arrhythmias.[1] |
| ln Vivo |
Tumor burden was significantly reduced by 69.2% when propafenone (20 mg/kg; intraperitoneally injected every other day) was administered [3]. Additionally, tumor cell proliferation was significantly reduced (average index dropped from 56.3±6.7% in the DMSO-treated group to 20.7±5.1% in the 10 mg/kg propafenone-treated group and from 20.7±5.1% in the 20 mg/kg propafenone-treated group to 11.3±4.0%. treatment group) [3]. In 14 normal human subjects, treatment with propafenone (150, 225, and 300 mg every eight hours for five days each) produced beta-blockade, as measured by the reduction in tachycardia induced by isoproterenol boluses and treadmill exercise. The degree of beta-blockade varied with the metabolizer phenotype. At lower dosages (150 and 225 mg), subjects with the poor-metabolizer phenotype (n=5) exhibited significantly greater beta-blockade compared to those with the extensive-metabolizer phenotype (n=9). At the highest dose (300 mg), a similar degree of beta-blockade was observed in both groups.[1] The beta-blocking effect of propafenone in vivo was correlated with its plasma concentration. A 10% reduction in maximal exercise heart rate was estimated to occur at plasma propafenone concentrations of approximately 3.12 ± 1.50 µmol/L (1065 ± 513 ng/mL) in extensive metabolizers and 3.30 ± 1.10 µmol/L (1126 ± 377 ng/mL) in poor metabolizers.[1] Prolongation of the QRS complex, an in vivo marker of sodium-channel blockade, was more prominent at any given plasma concentration of propafenone in subjects with the extensive-metabolizer phenotype than in those with the poor-metabolizer phenotype, suggesting metabolites contribute to sodium-channel blockade.[1] |
| Cell Assay |
Cell proliferation assay[3] Cell Types: Human esophageal squamous cell carcinoma lines KYSE30, KYSE150 and KYSE270 Tested Concentrations: 5, 10, 15, 20 and 25 μm Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Cells over time Proliferation gradually diminished in KYSE30, KYSE150 and KYSE270 cells, and cell proliferation was effectively inhibited with increasing concentration. Western Blot Analysis [3] Cell Types: Human ESCC cell lines KYSE30, KYSE150 and KYSE270 Tested Concentrations: 0, 10 and 20 μm Incubation Duration: 72 hrs (hours) Experimental Results: A significant down-regulation of Bcl-xL and Bcl-2 expression levels was observed. The affinity of propafenone and its metabolites for beta-adrenergic receptors was assessed using a radioligand binding assay on human lymphocytes. Lymphocytes were presumably isolated from human blood. The specific binding of the radioligand 125I-iodopindolol to β2-adrenoceptors on these cells was measured in the presence of increasing concentrations of propafenone, N-desalkyl propafenone, or 5-hydroxy propafenone. Displacement curves were generated, and IC50 values (concentration inhibiting 50% of specific binding) were determined. The dissociation constant (Ki) was also calculated. The shape of the curves was analyzed to be monophasic.[1] |
| Animal Protocol |
Animal/Disease Models: Female BALB/c nude mice (6-8 weeks) carrying KYSE270 xenografts [3] Doses: 10 mg/kg or 20 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results:Significant effect on tumor growth Inhibitory xenografts. Tumor Xenograft Model: Female BALB/c nude mice (6-8 weeks old) were subcutaneously implanted with KYSE270 cells (5 × 10⁵ cells in a mixture of PBS and Matrigel) to establish tumor xenografts. When tumors reached approximately 5 mm in diameter, mice were randomly divided into control and treatment groups. The treatment groups received intraperitoneal injections of propafenone at doses of 10 mg/kg or 20 mg/kg every other day. The control group received vehicle only. Body weight and tumor size (measured every three days, volume calculated as length × width² / 2) were monitored. At the end of the study, tumors and vital organs (lungs, liver, kidneys) were collected for further analysis (immunohistochemistry, Western blot, histological examination). [3] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion 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). Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets. 252 L In patients with ventricular arrhythmias and the extensive-metabolizer phenotype receiving 337.5, 450, 675, or 900 mg of propafenone hydrochloride daily (immediate-release tablets), the proportions of 5-hydroxypropafenone (5-OHP) to propafenone in plasma were 45, 40, 24, or 19%, respectively, while a subset of patients with the poor-metabolizer phenotype had higher relative plasma concentrations of the parent drug at each dosage and no detectable 5-OHP. Ratios of N-depropylpropafenone (NDPP) to propafenone are similar in extensive and poor metabolizers (approximately 10 and 6%, respectively). In poor metabolizers, NDPP is the principal metabolite and 5-OHP may not be detectable. Following oral administration of propafenone hydrochloride 300 mg (immediate-release tablets) every 8 hours for 14 days, plasma propafenone, 5-OHP, and NDPP concentrations averaged 1010, 174, and 179 ng/mL, respectively, in healthy individuals with the extensive-metabolizer phenotype. In an individual presumed to have the poor-metabolizer phenotype, plasma concentrations of propafenone, 5-OHP, and NDPP concentrations were 1048, undetectable, and 219 ng/mL, respectively, following oral administration of immediate-release tablets. Following administration of extended-release capsules of propafenone hydrochloride, plasma concentrations of 5-OHP and NDPP are generally less than 40 and 10% of plasma propafenone concentrations, respectively. The pattern of plasma concentrations of propafenone and its metabolites observed in an individual patient with long-term oral propafenone therapy depends principally on the genetically determined metabolizer phenotype and, to a lesser extent, on hepatic blood flow and enzyme function. Following oral administration of propafenone (immediate-release tablets), steady-state plasma concentrations of the parent drug and its metabolites are attained within 4-5 days in individuals with normal hepatic and renal function. Plasma concentrations of 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP) generally average less than 20% those of propafenone. Poor metabolizers achieve plasma propafenone concentrations 1.5-2 times higher than those of extensive metabolizers at propafenone hydrochloride dosages of 675-900 mg (immediate-release tablets) daily; at lower dosages, poor metabolizers may attain plasma propafenone concentrations more than fivefold higher than those of extensive metabolizers. The considerable degree of interindividual variability observed in the pharmacokinetics of propafenone in individuals with the extensive-metabolizer phenotype is principally attributable to first-pass hepatic metabolism and non-linear pharmacokinetics. The degree of interindividual variability in propafenone pharmacokinetic parameters is increased following single and multiple dose administration of propafenone hydrochloride extended-release capsules. The fact that interindividual variability in the pharmacokinetics of propafenone appears to be substantially less in individuals with the poor-metabolizer phenotype than in those with the extensive-metabolizer phenotype suggests that such variability may be due to CYP2D6 polymorphism rather than to the formulation. In healthy individuals, administration of propafenone hydrochloride as a single oral (300 or 450 mg immediate-release tablet) or IV (35-50 mg) dose produced similar peak plasma concentrations of the parent drug (278 versus 295 ng/mL, respectively). However, neither 5-hydroxypropafenone (5-OHP) nor N-depropylpropafenone (NDPP) was detectable in plasma after IV administration in these individuals. Since 5-OHP and NDPP has clinically important antiarrhythmic activity, propafenone's effect may differ with oral versus IV administration. Considerable interindividual variation exists in plasma concentrations of propafenone and its metabolites with a given dosage. Peak plasma concentrations of 5-OHP and NDPP average 101-288 and 8-40 ng/mL, respectively, in healthy individuals after administration of a single oral dose (300-450 mg) of propafenone hydrochloride immediate-release tablets. Propafenone, 5-OHP, and NDPP exhibit nonlinear pharmacokinetics in patients with the extensive-metabolizer phenotype, although the pharmacokinetics of 5-OHP and NDPP deviate from linearity only to a small extent. The pharmacokinetic profiles of propafenone, 5-OHP, and NDPP apparently are not affected substantially by age or gender. For more Absorption, Distribution and Excretion (Complete) data for Propafenone (15 total), please visit the HSDB record page. Metabolism / Metabolites 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. In individuals with the extensive-metabolizer phenotype, propafenone is metabolized in the liver to 2 active metabolites and at least 9 additional metabolites. The 2 active metabolites, 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP), are formed through hydroxylation and dealkylation of the parent drug. Propafenone hydroxylation via cytochrome CYP2D6, a cytochrome P-450 isoenzyme under genetic control, produces 5-OHP. Formation of NDPP is catalyzed by different isoenzymes, cytochrome CYP1A2 and CYP3A4. Differences in metabolism between R- and S-propafenone related to stereoselective interaction with the CYP2D6 isoenzyme have been observed in animals and humans receiving single enantiomers of the drug. Following a 250 mg oral dose of R- or S-propafenone hydrochloride administered to adults with the extensive-metabolizer phenotype, the mean values for elimination half-life, clearance, and volume of distribution for R-propafenone were smaller than those for S-propafenone, while AUC was larger; however, these stereospecific effects were not observed in an adult with the poor-metabolizer phenotype who received the separate drug enantiomers. In vitro and in vivo studies indicate that the R-enantiomer is cleared faster than the S-enantiomer via the 5-hydroxylation pathway (CYP2D6). This results in a higher ratio of the S-enantiomer to R-enantiomer at steady state. Although the enantiomers have equivalent sodium-channel blocking potency, the S-enantiomer is a more potent beta-adrenergic antagonist than the R-enantiomer. Following administration of propafenone hydrochloride (immediate-release tablets or extended-release capsules), the observed ratio of S-enantiomer to R-enantiomer (S/R ratio) for AUC was approximately 1.7. The S/R ratios after administration of 225, 325, or 425 mg extended-release capsules were independent of dose. In addition, similar S/R ratios were observed among metabolizer genotypes and following long-term administration There are two principal patterns of propafenone metabolism. These patterns are genetically determined by an individual's ability to metabolize the drug via a hepatic oxidation pathway. The ability to oxidatively metabolize propafenone is dependent on an individual's ability to metabolize debrisoquin (debrisoquin phenotype). The debrisoquin phenotype or the observed pattern of propafenone metabolites may be used to determine an individual's metabolic phenotype for propafenone. Individuals who extensively metabolize propafenone via the oxidation pathway exhibit the extensive-metabolizer phenotype, while those who have an impaired ability to metabolize the drug by this pathway exhibit the poor-metabolizer phenotype. Approximately 90-95% of Caucasians exhibit the extensive-metabolizer phenotype, with the remainder being poor metabolizers. Propafenone metabolism in patients with the poor-metabolizer phenotype is characterized by a linear dose-concentration relationship and a relatively long terminal elimination half-life; these individuals have increased plasma propafenone concentrations relative to individuals with the extensive-metabolizer phenotype and are more likely to experience beta-adrenergic blocking and adverse effects of the drug. Propafenone has known human metabolites that include 5-Hydroxypropafenone and N-Despropylpropafenone. Biological Half-Life 2-10 hours Following single or multiple oral doses of immediate-release tablets in adults with the extensive-metabolizer phenotype and normal renal and hepatic function, the elimination half-life of propafenone averages about 1-3 hours (range: 2-10 hours). The half-life of propafenone averages approximately 8-13 hours (range: 6-36 hours) in adults with the poor-metabolizer phenotype. Following a single oral dose of 300 mg of propafenone hydrochloride as immediate-release tablets, a half-life of 3.5 hours was reported; after administration of 300 mg of propafenone hydrochloride daily for 1 and 3 months, the reported half-lives were 6.7 and 5.8 hours, respectively. Steady-state plasma elimination half-life of propafenone is prolonged in poor metabolizers, averaging 17.2 hours (range: 10-32 hours) compared with 5.5 hours (range: 2-10 hours) in extensive metabolizers. Propafenone undergoes polymorphic metabolism in humans, primarily mediated by the hepatic cytochrome P450 isozyme P-450dbl (CYP2D6). Approximately 7% of the U.S. population are poor metabolizers with deficient activity of this enzyme.[1] Propafenone is biotransformed to two major active metabolites: 5-hydroxypropafenone and N-desalkyl propafenone (N-depropylpropafenone). The formation of 5-hydroxypropafenone is catalyzed by CYP2D6.[1] In poor metabolizers, the biotransformation of propafenone to 5-hydroxypropafenone is severely impaired. This results in significantly higher steady-state plasma concentrations of the parent propafenone and N-desalkyl propafenone, and much lower or undetectable levels of 5-hydroxypropafenone compared to extensive metabolizers. For example, after a 150 mg dose every 8 hours, trough plasma propafenone concentration was 0.56 ± 0.54 µmol/L in extensive metabolizers vs. 3.18 ± 0.76 µmol/L in poor metabolizers. 5-Hydroxypropafenone was not detected (ND) in poor metabolizers.[1] In extensive metabolizers, the propafenone plasma concentration increased disproportionately with dose, suggesting the CYP2D6 metabolic pathway is saturable. In poor metabolizers, the plasma propafenone level increased in a more linear fashion with dose.[1] The metabolism of propafenone can be shunted to N-dealkylation in poor metabolizers, as evidenced by elevated N-desalkyl propafenone levels in this group.[1] |
| Toxicity/Toxicokinetics |
Hepatotoxicity In clinical trials, propafenone was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Since its approval and more widescale use, propafenone has been linked to rare instances of clinically apparent liver injury, at least a dozen cases of which have been reported in the literature. Patients usually present with symptoms of jaundice and pruritus 2 to 8 weeks after starting propafenone, and the pattern of serum enzyme elevations are typically mixed (Case 1) or cholestatic (Case 2). Immunoallergic and autoimmune features are uncommon. While the jaundice can be prolonged, patients typically recover in 1 to 3 months and there have been no instances of acute liver failure, chronic hepatitis or vanishing bile duct syndrome attributed to its use. Likelihood score: B (rare but likely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Limited information indicates that maternal doses of propafenone up to 900 mg daily produce low levels in milk. If propafenone is required by the mother it is not a reason to discontinue breastfeeding. Until more data become available, propafenone should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 97% Interactions Although specific pharmacokinetic drug interaction studies are not available, the manufacturer of propafenone states that the drug should not be used concomitantly with other drugs that prolong the QT interval, including certain phenothiazines, cisapride, bepridil (not currently commercially available in the US), tricyclic antidepressant agents, or macrolides. Although specific pharmacokinetic drug interaction studies are not available, the manufacturer of ritonavir states that ritonavir should not be used concomitantly with certain cardiovascular agents, including propafenone, because of the potential for substantially increased plasma concentrations of these cardiovascular drugs and potentially serious and/or life-threatening adverse effects. This pharmacokinetic interaction may occur because ritonavir has high affinity for several cytochrome P-450 (CYP) isoenzymes (e.g., CYP3A, CYP2D6, CYP1A2) involved in propafenone metabolism. Increased serum theophylline concentrations have been reported in patients receiving theophylline concomitantly with propafenone and some clinicians suggest that serum theophylline concentrations and ECGs be monitored closely in patients receiving such combined therapy. The manufacturer states that concomitant use of propafenone and local anesthetic agents (i.e., during pacemaker implantation, surgery, or dental procedures) may increase the risk of adverse nervous system effects. For more Interactions (Complete) data for Propafenone (24 total), please visit the HSDB record page. Non-Human Toxicity Values LD50 Dogt iv 10 mg/kg /Propafenone hydrochloride/ LD50 Rat iv 18,800 ug/kg /Propafenone hydrochloride/ LD50 Rat oral 700 mg/kg /Propafenone hydrochloride/ Side effects are reported to be significantly more frequent when trough plasma propafenone concentrations exceed 2.64 µmol per liter (900 ng per milliliter). Such elevated concentrations occur more frequently in subjects with the poor-metabolizer phenotype.[1] Clinically significant beta-blockade from propafenone, which may be considered a side effect in some contexts (e.g., in patients with asthma), occurs inconsistently in vivo and is more pronounced in poor metabolizers due to higher parent drug accumulation.[1] No changes in FEV1 (a measure of lung function) were found in the normal subjects studied, despite the beta-blocking effects observed.[1] |
| References |
[1]. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med. 1990 Jun 21;322(25):1764-8. [2]. Effects of propafenone on K currents in human atrial myocytes. Br J Pharmacol. 1999 Mar;126(5):1153-62. [3]. Propafenone suppresses esophageal cancer proliferation through inducing mitochondrial dysfunction. Am J Cancer Res. 2017 Nov 1;7(11):2245-2256. |
| Additional Infomation |
Therapeutic Uses Anti-Arrhythmia Agents When given as immediate-release tablets, propafenone hydrochloride is used to prolong the time to recurrence of symptomatic, disabling paroxysmal supraventricular tachycardia (PSVT) (e.g., atrioventricular (AV) nodal reentrant tachycardia or AV reentrant tachycardia ( Wolff-Parkinson-White syndrome)) and symptomatic, disabling paroxsymal atrial fibrillation/flutter (PAF) in patients without structural heart disease. While comparative studies are limited, propafenone appears to be comparable to other antiarrhythmic agents (e.g., quinidine, disopyramide, flecainide, procainamide, sotalol) in preventing recurrences of PAF and maintaining sinus rhythm following successful cardioversion of atrial fibrillation. /Included in US product label/ When given as extended-release capsules, propafenone is used to prolong the time to recurrence of symptomatic paroxysmal atrial fibrillation in patients without structural heart disease.289 The safety and efficacy of propafenone as extended-release capsules have not been established in patients with exclusively PSVT or atrial flutter. /Included in US product label/ Propafenone hydrochloride (immediate-release tablets) is used orally to suppress and prevent the recurrence of documented life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation). Based on the results of the Cardiac Arrhythmia Suppression Trial (CAST), the US Food and Drug Administration (FDA), the manufacturer, and many clinicians recommend that therapy with antiarrhythmic agents, including propafenone, be reserved for the suppression and prevention of documented ventricular tachyarrhythmias that, in the clinician's judgment, are considered life-threatening. /Included in US product label/ For more Therapeutic Uses (Complete) data for Propafenone (10 total), please visit the HSDB record page. Drug Warnings In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously, an increased rate of death or reversed cardiac arrest rate (7.7%; 56/730) was seen in patients treated with encainide or flecainide (Class 1C antiarrhythmics) compared with that seen in patients assigned to placebo (3.0%; 22/725). The average duration of treatment with encainide or flecainide in this study was ten months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmic drugs is uncertain, but at present it is prudent to consider any 1C antiarrhythmic to have a significant risk in patients with structural heart disease. Given the lack of any evidence that these drugs improve survival, antiarrhythmic agents should generally be avoided in patients with non-life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. The most common adverse effects of propafenone involve the GI, cardiovascular, and central nervous systems and generally are dose related. Discontinuance of propafenone therapy was required in about 20% of patients receiving the drug in clinical trials. Drug discontinuance in patients treated for ventricular arrhythmias was required most frequently (i.e., in greater than 1% of patients) for proarrhythmia (4.7%), nausea and/or vomiting (3.4%), dizziness (2.4%), dyspnea (1.6%), congestive heart failure (1.4%), and ventricular tachycardia (1.2%). In patients treated for supraventricular arrhythmias in clinical trials, discontinuance of therapy was required most frequently (i.e., in greater than 1% of patients) for nausea and/or vomiting (2.9%), wide-complex tachycardia (1.9%), dizziness (1.7%), fatigue (1.5%), unusual taste (1.3%), and weakness (1.3%). Adverse nervous system effects reported in US clinical trials in patients receiving propafenone for the treatment of ventricular arrhythmias included dizziness and/or lightheadedness of patients, fatigue/lethargy in 6%, and headache in 5%.1 Weakness, ataxia, insomnia, or anxiety was reported in 2%, and tremor or drowsiness in 1% of patients receiving propafenone for ventricular arrhythmias. Pain or loss of balance also has been reported with propafenone therapy in patients with ventricular arrhythmias. Transient global amnesia, which resolved within hours after drug discontinuance, has been reported in at least one patient receiving propafenone. Peripheral neuropathy, which was characterized by episodic jabbing and crushing pain in the hands and feet and hyperesthesia of the extremities and resolved following discontinuance of the drug, has been reported rarely with propafenone therapy. For more Drug Warnings (Complete) data for Propafenone (31 total), please visit the HSDB record page. 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 acts by inhibiting sodium channels to restrict the entry of sodium into cardiac cells resulting in reduced excitation. Propafenone has local anesthetic activity approximately equal to procaine. Propafenone is a class Ic antiarrhythmic agent with sodium-channel blocking activity and structural similarity to propranolol. It is used in the management of atrial and ventricular arrhythmias.[1] The extent of beta-blockade during propafenone therapy is highly variable among individuals and is largely determined by genetic polymorphisms in CYP2D6, which affect the drug's metabolism. Poor metabolizers experience enhanced beta-blockade due to higher systemic exposure to the parent drug, which is the primary mediator of this effect.[1] The beta-blocking effect of propafenone may contribute to both its antiarrhythmic efficacy and the genesis of certain side effects.[1] The sodium-channel blocking effect of propafenone is contributed to by both the parent drug and its active metabolite 5-hydroxypropafenone, which has equal or greater potency in this regard.[1] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9287 mL | 14.6434 mL | 29.2869 mL | |
| 5 mM | 0.5857 mL | 2.9287 mL | 5.8574 mL | |
| 10 mM | 0.2929 mL | 1.4643 mL | 2.9287 mL |