β-adrenergic receptor; Potassium channels

Sotalol hydrochloride (MJ 1999) is an agent of antiarrhythmic. The electroconvulsive threshold remains unaffected by sotalol at doses up to 100 mg/kg. When administered at doses ranging from 80-100 mg/kg, sotalol hydrochloride does not impede the antielectroshock properties of topiramate, lamotrigine, oxcarbazepine, or pregabalin. Neither long-term memory nor motor function are hampered by sotalol hydrochloride, either by itself or in combination with antiepileptic medications. Lamotrigine's brain concentration is greatly reduced by sotalol hydrochloride (100 mg/kg), while topiramate and oxcarbazepine's concentrations are increased. Pregabalin levels are unaffected[3].

Class II antiarrhythmics or β-blockers are antisympathetic nervous system agents that act by blocking β-adrenoceptors. Despite their common clinical use, little is known about the effects of β-blockers on free intracellular calcium (Ca2+ i), an important cytosolic second messenger and a key regulator of cell function. We investigated the role of four chemical analogs, commonly prescribed β-blockers (atenolol, metoprolol, propranolol, and sotalol), on Ca2+ i release and whole-cell currents in mammalian cancer cells (PC3 prostate cancer and MCF7 breast cancer cell lines). We discovered that only propranolol activated free Ca2+ i release with distinct kinetics, whereas atenolol, metoprolol, and sotalol did not. The propranolol-induced Ca2+ i release was significantly inhibited by the chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) and by dantrolene, an inhibitor of the endoplasmic reticulum (ER) ryanodine receptor channels, and it was completely abolished by 2-aminoethoxydiphenyl borate, an inhibitor of the ER inositol-1,4,5-trisphosphate (IP3) receptor channels. Exhaustion of ER stores with 4-chloro-m-cresol, a ryanodine receptor activator, or thapsigargin, a sarco/ER Ca2+ ATPase inhibitor, precluded the propranolol-induced Ca2+ i release. Finally, preincubation of cells with sotalol or timolol, nonselective blockers of β-adrenoceptors, also reduced the Ca2+ i release activated by propranolol. Our results show that different β-blockers have differential effects on whole-cell currents and free Ca2+ i release and that propranolol activates store-operated Ca2+ i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP3 The differential action of class II antiarrhythmics on Ca2+ i release may have implications on the pharmacology of these drugs[1].

20-25 g female Swiss mice
100 mg/kg
Administered intraperitoneally

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Drugs[3]
Sotalol (SOT), an antiarrhythmic drug, and four second-generation antiepileptic medications, i.e., oxcarbazepine (OXC), lamotrigine (LTG), pregabalin (PGB), and topiramate (TPM), were used in the study. All drugs were suspended in 1% solution of Tween 80, prepared freshly on each day of tests, and administered intraperitoneally in a volume of 10 ml/kg of body weight 30 (oxcarbazepine), 60 (sotalol and lamotrigine), 60 (topiramate), and 120 min (pregabalin) before the tests. Maximal electroshock seizure test in mice[3]
The maximal electroshock (MES) test is a widely used preclinical model of tonic–clonic seizures. Step-by-step procedures were described previously by Borowicz et al. [14]. The antielectroshock activity of antiepileptic drugs applied alone and in combinations with sotalol was determined as their ability to protect 50% of mice against tonic hindlimb extension induced by 25 mA electric current delivered by ear-clip electrodes. The dose–response curves were constructed based on the percentage of mice protected and the respective median effective doses (ED50 values in mg/kg) were evaluated.

[1]. Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines. J Pharmacol Exp Ther. 2019 Apr;369(1):152-162.

[2]. Pediatric Dosing of Intravenous Sotalol Based on Body Surface Area in Patients with Arrhythmia. Pediatr Cardiol. 2017 Oct;38(7):1450-1455.

[3]. Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice.Pharmacol Rep. 2021 Apr;73(2):516-524.

Sotalol hydrochloride is a hydrochloride salt that is the monohydrochloride of sotalol. It has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. It is used (usually as the hydrochloride salt) for the management of ventricular and supraventricular arrhythmias. It has a role as a beta-adrenergic antagonist and an anti-arrhythmia drug. It contains a sotalol(1+).
Sotalol Hydrochloride is the hydrochloride salt form of sotalol, an ethanolamine derivative with Class III antiarrhythmic and antihypertensive properties. Sotalol hydrochloride is a nonselective beta-adrenergic receptor and potassium channel antagonist. In the heart, this agent inhibits chronotropic and inotropic effects thereby slowing the heart rate and decreasing myocardial contractility. This agent also reduces sinus rate, slows conduction in the atria and in the atrioventricular (AV) node and increases the functional refractory period of the AV node. In the lungs, sotalol inhibits vasodilation and bronchodilation. In addition, this agent inhibits renin release.
An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias.

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In a recently published study, we evaluated the efficacy and safety of intravenous sotalol in pediatric patients with incessant tachyarrhythmias and we have found that intravenous sotalol is effective and safe. Our dosing regimen was based on the body weight of the patients. In the US, the recommendation for intravenous sotalol dosing in pediatric patients is based on body surface area (BSA) while taking into consideration the patients' age. The purpose of this paper is to show the correspondence of a body weight-based dosing regimen when expressed for BSA as mg/m2. We evaluated the similarity of a body weight-based dose to that calculated based on BSA using the US labeling recommendations. Of the 83 patients, 5 were newborns (age: 0-30 days), 39 infants and toddlers (age: 1-24 month), 26 young children (age: >2-6 years), 11 older children (age: 6-12 years), and 2 adolescents (age: 14 years). Each received a loading dose of 1 mg/kg intravenous sotalol administered over 10 min followed by a maintenance dose of 4.5 mg/kg/day. There was a close correlation between the sotalol loading doses calculated based on body weight and BSA across the entire age range (r = 0.977, p < 0.001). In most of the age groups, the body weight-based loading doses were lower or equal to the BSA-based doses. Only in the adolescents were the body weight-based doses higher. The maintenance doses given in our study were significantly higher than the BSA-based dose in newborns: 75 ± 6 versus 53 ± 8 mg/m2, p < 0.05; infants/toddlers: 88 ± 14 versus 77 ± 7 mg/m2, p < 0.001; younger children: 113 ± 12 versus 85 mg/m2, p < 0.001; older children: 123 ± 16 versus 85 mg/m2, p < 0.01; and adolescents 157 ± 30 versus 85.5 mg/m2. Despite the rapid administration of the loading dose and the increased maintenance doses, our body weight-based dosing regimen was safe. Only one newborn had significant adverse event (AV block) that resolved spontaneously after discontinuation of the infusion.[2]

C12H21CLN2O3S

308.82

308.1

C, 46.67; H, 6.85; Cl, 11.48; N, 9.07; O, 15.54; S, 10.38

959-24-0

Sotalol; 3930-20-9

66245

White to off-white solid powder

443.3ºC at 760 mmHg

218-220°C

221.9ºC

3.44

86.81

CC(C)NCC(C1=CC=C(C=C1)NS(=O)(=O)C)O.Cl

VIDRYROWYFWGSY-UHFFFAOYSA-N

InChI=1S/C12H20N2O3S.ClH/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;1H

N-[4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl]methanesulfonamide;hydrochloride

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.10 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.10 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.10 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.

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Solubility in Formulation 4: 110 mg/mL (356.19 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)