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Identification
Name Sotalol
Accession Number DB00489 (APRD01230)
Type small molecule
Groups approved
Description

An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Sotalol HCL
Salts Not Available
Brand names
Name Company
Betapace
Betapace AF
Sorine
Brand mixtures Not Available
Categories
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Anti-Arrhythmia Agents
CAS number 3930-20-9
Weight Average: 272.364
Monoisotopic: 272.119463206
Chemical Formula C12H20N2O3S
InChI Key InChIKey=ZBMZVLHSJCTVON-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
N-(4-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}phenyl)methanesulfonamide
SMILES
CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Phenethylamines
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Aliphatic and Aryl Amines
  • Sulfonyls
  • Benzene and Derivatives
  • Amino Alcohols
  • Phenethylamines
  • Aromatic compounds
  • Sulfonamides
  • Alcohols and Polyols
  • Anilines
Pharmacology
Indication For the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm. Also for the treatment of documented life-threatening ventricular arrhythmias.
Pharmacodynamics Sotalol is an antiarrhythmic drug. It falls into the class of beta blockers (and class II antiarrhythmic agents) because of its primary action on the β-adrenergic receptors in the heart. In addition to its actions on the beta receptors in the heart, sotalol inhibits the inward potassium ion channels of the heart. In so doing, sotalol prolongs repolarization, therefore lengthening the QT interval and decreasing automaticity. It also slows atrioventricular (AV) nodal conduction. Because of these actions on the cardiac action potential, it is also considered a class III antiarrhythmic agent. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80mg/day and maximal at doses between 320 and 640 mg/day. Sotalol does not have partial agonist or membrane stabilizing activity. Although significant beta-blockade occurs at oral doses as low as 25 mg, significant Class Ieffects are seen only at daily doses of 160 mg and above.
Mechanism of action Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class I) and cardiac action potential duration prolongation (Vaughan Williams Class I) antiarrhythmic properties. Sotalol is a racemic mixture of d- and l-sotalol. Both isomers have similar Class I antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity. Sotalol inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium and β2-adrenergic receptors within bronchial and vascular smooth muscle. The electrophysiologic effects of sotalol may be due to its selective inhibition of the rapidly activating component of the potassium channel involved in the repolarization of cardiac cells. The class II electrophysiologic effects are caused by an increase in sinus cycle length (slowed heart rate), decreased AV nodal conduction, and increased AV nodal refractoriness, while the class III electrophysiological effects include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways (where present) in both the anterograde and retrograde directions.
Absorption In healthy subjects, the oral bioavailability of sotalol is 90-100%. Absorption is reduced by approximately 20% compared to fasting when administered with a standard meal.
Volume of distribution Not Available
Protein binding Sotalol does not bind to plasma proteins.
Metabolism Sotalol is not metabolized.
Route of elimination Excretion is predominantly via the kidney in the unchanged form. Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk.
Half life Mean elimination half-life is 12 hours. Impaired renal function in geriatric patients can increase the terminal elimination half-life.
Clearance Not Available
Toxicity The most common signs to be expected are bradycardia, congestive heart failure, hypotension, bronchospasm and hypoglycemia. In cases of massive intentional overdosage (2-16 grams) of sotalol the following clinical findings were seen: hypotension, bradycardia, cardiac asystole, prolongation of QT interval, Torsade de Pointes, ventricular tachy-cardia, and premature ventricular complexes.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Academic pharmaceuticals inc
  • Bayer healthcare pharmaceuticals inc
  • Upsher smith laboratories inc
  • Amneal pharmaceutical
  • Apotex inc
  • Apotex inc etobicoke site
  • Impax pharmaceuticals
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Betapace AF 100 160 mg tablet Box 538.2 USD box
Betapace AF 60 120 mg tablet Bottle 311.06 USD bottle
Betapace 240 mg tablet 8.94 USD tablet
Sotalol hcl 150 mg/10 ml vial 7.8 USD ml
Betapace 160 mg tablet 6.87 USD tablet
Betapace af 160 mg tablet 6.24 USD tablet
Sorine 240 mg tablet 5.6 USD tablet
Betapace 120 mg tablet 5.5 USD tablet
Sotalol HCl 240 mg tablet 5.29 USD tablet
Sotalol 240 mg tablet 5.09 USD tablet
Betapace af 120 mg tablet 4.99 USD tablet
Sotalol HCl (AF) 160 mg tablet 4.45 USD tablet
Sorine 160 mg tablet 4.31 USD tablet
Sotalol af 160 mg tablet 4.27 USD tablet
Betapace 80 mg tablet 4.12 USD tablet
Sotalol HCl 160 mg tablet 4.07 USD tablet
Sotalol 160 mg tablet 3.92 USD tablet
Betapace af 80 mg tablet 3.74 USD tablet
Sotalol HCl (AF) 120 mg tablet 3.56 USD tablet
Sorine 120 mg tablet 3.46 USD tablet
Sotalol af 120 mg tablet 3.42 USD tablet
Sotalol HCl 120 mg tablet 3.26 USD tablet
Sotalol 120 mg tablet 3.13 USD tablet
Sotalol HCl 80 mg tablet 2.67 USD tablet
Sotalol HCl (AF) 80 mg tablet 2.67 USD tablet
Sorine 80 mg tablet 2.61 USD tablet
Sotalol af 80 mg tablet 2.56 USD tablet
Sotalol 80 mg tablet 2.35 USD tablet
Apo-Sotalol 160 mg Tablet 0.68 USD tablet
Co Sotalol 160 mg Tablet 0.68 USD tablet
Mylan-Sotalol 160 mg Tablet 0.68 USD tablet
Novo-Sotalol 160 mg Tablet 0.68 USD tablet
Nu-Sotalol 160 mg Tablet 0.68 USD tablet
Pms-Sotalol 160 mg Tablet 0.68 USD tablet
Ratio-Sotalol 160 mg Tablet 0.68 USD tablet
Sandoz Sotalol 160 mg Tablet 0.68 USD tablet
Apo-Sotalol 80 mg Tablet 0.62 USD tablet
Co Sotalol 80 mg Tablet 0.62 USD tablet
Mylan-Sotalol 80 mg Tablet 0.62 USD tablet
Novo-Sotalol 80 mg Tablet 0.62 USD tablet
Nu-Sotalol 80 mg Tablet 0.62 USD tablet
Pms-Sotalol 80 mg Tablet 0.62 USD tablet
Ratio-Sotalol 80 mg Tablet 0.62 USD tablet
Sandoz Sotalol 80 mg Tablet 0.62 USD tablet
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Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 206.5-207 °C PhysProp
water solubility Soluble (5510 mg/L) Not Available
logP 0.24 BURGOT,G ET AL. (1990)
Predicted Properties
Property Value Source
water solubility 7.82e-01 g/l ALOGPS
logP 0.85 ALOGPS
logP -0.4 ChemAxon
logS -2.5 ALOGPS
pKa (strongest acidic) 10.07 ChemAxon
pKa (strongest basic) 9.43 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 78.43 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 71.12 ChemAxon
polarizability 29.34 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP: Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet. 1996 Jul 6;348(9019):7-12. Pubmed
External Links
Resource Link
KEGG Compound C07309 Link_out
PubChem Compound 5253 Link_out
PubChem Substance 46505012 Link_out
ChemSpider 5063 Link_out
BindingDB 25762 Link_out
Therapeutic Targets Database DAP000372 Link_out
PharmGKB PA451457 Link_out
Drug Product Database 2257858 Link_out
RxList http://www.rxlist.com/cgi/generic/betapaceaf.htm Link_out
Drugs.com http://www.drugs.com/cdi/sotalol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Sotalol Link_out
ATC Codes
  • C07AA07
  • C07AA57
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label show (93.8 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acetohexamide The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Aminophylline Antagonism of action and increased effect of theophylline
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Chlorpropamide The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Clonidine Increased hypertension when clonidine stopped
Dihydroergotamine Ischemia with risk of gangrene
Disopyramide The beta-blocker, sotalol, may increase the toxicity of disopyramide.
Epinephrine Hypertension, then bradycardia
Ergotamine Ischemia with risk of gangrene
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Fenoterol Antagonism
Fingolimod Pharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
Formoterol Antagonism
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Gliclazide The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Glyburide The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Ibuprofen Risk of inhibition of renal prostaglandins
Indomethacin Risk of inhibition of renal prostaglandins
Insulin The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Insulin Glargine The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Methyldopa Possible hypertensive crisis
Methysergide Ischemia with risk of gangrene
Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
Orciprenaline Antagonism
Oxtriphylline Antagonism of action and increased effect of theophylline
Pipobroman Antagonism
Piroxicam Risk of inhibition of renal prostaglandins
Prazosin Risk of hypotension at the beginning of therapy
Ranolazine Possible additive effect on QT prolongation
Repaglinide The beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telithromycin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Terazosin Increased risk of hypotension. Initiate concomitant therapy cautiously.
Terbutaline Antagonism
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Theophylline Antagonism of action and increased effect of theophylline
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions Not Available
Targets

1. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: yes
Actions: inhibitor

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Shimizu W, Antzelevitch C: Effects of a K(+) channel opener to reduce transmural dispersion of repolarization and prevent torsade de pointes in LQT1, LQT2, and LQT3 models of the long-QT syndrome. Circulation. 2000 Aug 8;102(6):706-12. Pubmed
  2. Numaguchi H, Mullins FM, Johnson JP Jr, Johns DC, Po SS, Yang IC, Tomaselli GF, Balser JR: Probing the interaction between inactivation gating and Dd-sotalol block of HERG. Circ Res. 2000 Nov 24;87(11):1012-8. Pubmed
  3. Wolpert C, Schimpf R, Giustetto C, Antzelevitch C, Cordeiro J, Dumaine R, Brugada R, Hong K, Bauersfeld U, Gaita F, Borggrefe M: Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. Pubmed
  4. Wolpert C, Schimpf R, Veltmann C, Giustetto C, Gaita F, Borggrefe M: Clinical characteristics and treatment of short QT syndrome. Expert Rev Cardiovasc Ther. 2005 Jul;3(4):611-7. Pubmed
  5. Fedida D, Orth PM, Hesketh JC, Ezrin AM: The role of late I and antiarrhythmic drugs in EAD formation and termination in Purkinje fibers. J Cardiovasc Electrophysiol. 2006 May;17 Suppl 1:S71-S78. Pubmed

2. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lowe MD, Lynham JA, Grace AA, Kaumann AJ: Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium. Br J Pharmacol. 2002 Jan;135(2):451-61. Pubmed
  2. Joseph SS, Lynham JA, Colledge WH, Kaumann AJ: Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):525-32. Epub 2004 Apr 2. Pubmed
  3. Yalcin I, Choucair-Jaafar N, Benbouzid M, Tessier LH, Muller A, Hein L, Freund-Mercier MJ, Barrot M: beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25. Pubmed
  4. Doggrell SA: The effects of (/-)-, ()-, and (-)-atenolol, sotalol, and amosulalol on the rat left atria and portal vein. Chirality. 1993;5(1):8-14. Pubmed
  5. Juberg EN, Minneman KP, Abel PW: Beta 1- and beta 2-adrenoceptor binding and functional response in right and left atria of rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):193-202. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Beta-2 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lowe MD, Lynham JA, Grace AA, Kaumann AJ: Comparison of the affinity of beta-blockers for two states of the beta 1-adrenoceptor in ferret ventricular myocardium. Br J Pharmacol. 2002 Jan;135(2):451-61. Pubmed
  2. Joseph SS, Lynham JA, Colledge WH, Kaumann AJ: Binding of (-)-[3H]-CGP12177 at two sites in recombinant human beta 1-adrenoceptors and interaction with beta-blockers. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):525-32. Epub 2004 Apr 2. Pubmed
  3. Yalcin I, Choucair-Jaafar N, Benbouzid M, Tessier LH, Muller A, Hein L, Freund-Mercier MJ, Barrot M: beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25. Pubmed
  4. Doggrell SA: The effects of (/-)-, ()-, and (-)-atenolol, sotalol, and amosulalol on the rat left atria and portal vein. Chirality. 1993;5(1):8-14. Pubmed
  5. Juberg EN, Minneman KP, Abel PW: Beta 1- and beta 2-adrenoceptor binding and functional response in right and left atria of rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):193-202. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19