| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
β-adrenoceptor
The primary target of (+)-Sotalol is the cardiac potassium channel, specifically the rapid component of the delayed rectifier potassium current (IKr) encoded by hERG. Unlike the racemate or the (R)-enantiomer, (+)-Sotalol has minimal beta-adrenergic receptor blocking activity, making it a relatively pure class III antiarrhythmic agent that selectively prolongs action potential duration and refractoriness without significant beta-blockade. |
|---|---|
| ln Vitro |
In isolated myocardium, (+)-Sotalol (1, 10, 100 µM) prolongs action potentials [2]. The action potentials of three different cell types (endocardium, epicardium, midmyocardium, and transmural cells) are prolonged by (+)-Sotalol (100 μM, 60 minutes) [4].
In vitro, (+)-Sotalol potently blocks the hERG potassium channel, inhibiting the IKr current that is critical for cardiac repolarization. This blockade leads to prolongation of the action potential duration (APD) and effective refractory period (ERP) in isolated cardiac myocytes. Unlike the racemic mixture of sotalol, the (+)-enantiomer has negligible affinity for beta1- and beta2-adrenergic receptors, thus lacking class II antiarrhythmic activity. |
| ln Vivo |
(+)-Sotalol (8 mg/kg, intravenously) prevents ventricular tachycardia in dogs that is brought on by planned stimulation[3].
In vivo, (+)-Sotalol has demonstrated antiarrhythmic efficacy in various animal models (e.g., chloroform-induced arrhythmias, ouabain-induced arrhythmias) by prolonging ventricular repolarization. It is used as a research tool to dissect the contributions of IKr blockade versus beta-adrenergic antagonism to the antiarrhythmic and proarrhythmic effects of sotalol. Its pure class III profile distinguishes it from the racemate, which has both class II and class III activity. |
| Enzyme Assay |
A standard non-cellular protocol for IKr current measurement uses the patch-clamp technique. HEK-293 cells stably expressing the hERG potassium channel are voltage-clamped at a holding potential of -80 mV. A standard voltage protocol (e.g., depolarization to +20 mV for 5 seconds, repolarization to -40 mV) is applied to activate hERG currents. Various concentrations of (+)-Sotalol are applied, and the reduction in tail current amplitude is measured to calculate the IC50 for hERG channel blockade.
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| Cell Assay |
For functional cellular assays, isolated guinea pig or rabbit ventricular myocytes are used. Cells are subjected to whole-cell patch-clamp recording to measure action potential duration (APD) at 90% repolarization. (+)-Sotalol is superfused over the cell at increasing concentrations (e.g., 1-100 uM), and the prolongation of APD is measured. Lack of effect on isoproterenol-stimulated cAMP accumulation confirms minimal beta-adrenergic receptor blockade.
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| Animal Protocol |
Animal/Disease Models: Programmed stimulated Dogs[3]
Doses: 8 mg/kg Route of Administration: intravenous (iv) injection Experimental Results: Increased normal zone ventricular refractoriness, and prevent propagation of programmed ventricular extra-stimuli of sufficient prematurity to elicit tachyarrhythmias. In an in vivo animal protocol, male guinea pigs or dogs are anesthetized and instrumented for surface ECG recording. (+)-Sotalol is administered intravenously (e.g., 0.1-3 mg/kg) or orally, and the QT interval of the ECG is measured at baseline and at various time points post-dose. Prolongation of the QT interval indicates successful block of IKr channels and class III antiarrhythmic activity. Arrhythmia models (e.g., ischemia-reperfusion) can be used to assess antiarrhythmic efficacy. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for (+)-Sotalol in isolation is limited; however, the pharmacokinetics of racemic sotalol are well-characterized. Sotalol is orally bioavailable, with a half-life of approximately 12 hours in humans, and is primarily excreted unchanged by the kidneys. The (+)-enantiomer is expected to have a similar PK profile, allowing twice-daily dosing in clinical settings.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided for (+)-Sotalol specifically. As a class III antiarrhythmic agent, its primary toxicity is proarrhythmia, specifically torsade de pointes (TdP), a life-threatening polymorphic ventricular tachycardia, due to excessive prolongation of the QT interval. This risk is dose-dependent and is exacerbated by hypokalemia, bradycardia, and concomitant use of other QT-prolonging drugs.
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| References |
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| Additional Infomation |
(+)-Sotalol is a unique pharmacological tool because it separates the class II (beta-blockade) and class III (IKr blockade) activities of racemic sotalol. Unlabeled sotalol hydrochloride (Betapace) is a clinically approved antiarrhythmic agent used for the treatment of life-threatening ventricular arrhythmias and the maintenance of normal sinus rhythm in patients with atrial fibrillation. The stereochemistry of sotalol is critical: the (R)-enantiomer is a non-selective beta-blocker, while the (+)-(S)-enantiomer is the primary contributor to class III antiarrhythmic activity.
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| Molecular Formula |
C12H20N2O3S
|
|---|---|
| Molecular Weight |
272.36
|
| Exact Mass |
272.119
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| CAS # |
30236-32-9
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| PubChem CID |
119259
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| Appearance |
White to off-white solid powder
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| Density |
1.239g/cm3
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| Boiling Point |
443.3ºC at 760mmHg
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| Flash Point |
221.9ºC
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| Index of Refraction |
1.57
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| LogP |
2.634
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
18
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| Complexity |
330
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)NC[C@H](C1=CC=C(C=C1)NS(=O)(=O)C)O
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| InChi Key |
ZBMZVLHSJCTVON-GFCCVEGCSA-N
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| InChi Code |
InChI=1S/C12H20N2O3S/c1-9(2)13-8-12(15)10-4-6-11(7-5-10)14-18(3,16)17/h4-7,9,12-15H,8H2,1-3H3/t12-/m1/s1
|
| Chemical Name |
N-[4-[(1S)-1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl]methanesulfonamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (367.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.18 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 (9.18 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (9.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6716 mL | 18.3581 mL | 36.7161 mL | |
| 5 mM | 0.7343 mL | 3.6716 mL | 7.3432 mL | |
| 10 mM | 0.3672 mL | 1.8358 mL | 3.6716 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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