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Identification
NameSotalol
Accession NumberDB00489  (APRD01230)
Typesmall molecule
Groupsapproved
Description

An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
4'-(1-Hydroxy-2-(isopropylamino)ethyl)methane sulfonanilideNot AvailableNot Available
beta-CardoneNot AvailableNot Available
SotalolFrench/German/SpanishINN
SotaloloNot AvailableDCIT
SotalolumLatinINN
Salts
Name/CAS Structure Properties
Sotalol Hydrochloride
959-24-0
Thumb
  • InChI Key: VIDRYROWYFWGSY-UHFFFAOYNA-N
  • Monoisotopic Mass: 308.096140945
  • Average Mass: 308.825
DBSALT000318
Brand names
NameCompany
BetapaceBerlex
BiosotalSanofi-Aventis
CardolAlphapharm
DarobAbbott
Darob miteAbbott
HipecorMerck
LoritmikKrka
RytmobetaAbbott
SorineUpsher-Smith
SotacorBristol-Myers Squibb
SotagardGlaxoSmithKline
SotalexBristol-Myers Squibb
SotaporBristol-Myers Squibb
TalozinAdeka
Tan ShiChia Tai Tianqing
Xi An LinChangzhou Pharmaceutical Factory
Brand mixturesNot Available
CategoriesNot Available
CAS number3930-20-9
WeightAverage: 272.364
Monoisotopic: 272.119463206
Chemical FormulaC12H20N2O3S
InChI KeyZBMZVLHSJCTVON-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassSulfanilides
Direct parentSulfanilides
Alternative parentsSulfonyls; Sulfonamides; Secondary Alcohols; 1,2-Aminoalcohols; Dialkylamines; Polyamines
Substituentssulfonyl; sulfonamide; sulfonic acid derivative; 1,2-aminoalcohol; secondary alcohol; secondary amine; secondary aliphatic amine; polyamine; alcohol; amine; organonitrogen compound
Classification descriptionThis compound belongs to the sulfanilides. These are organic aromatic compounds containing a sulfanilide moiety, with the general structure RS(=O)(=O)NC1=CC=CC=C1.
Pharmacology
IndicationFor 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.
PharmacodynamicsSotalol 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 actionSotalol 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.
AbsorptionIn 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 distributionNot Available
Protein bindingSotalol does not bind to plasma proteins.
Metabolism

Sotalol is not metabolized.

Route of eliminationExcretion 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 lifeMean elimination half-life is 12 hours. Impaired renal function in geriatric patients can increase the terminal elimination half-life.
ClearanceNot Available
ToxicityThe 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
PathwayCategorySMPDB ID
Sotalol Action PathwayDrug actionSMP00660
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.995
Blood Brain Barrier + 0.9382
Caco-2 permeable - 0.8957
P-glycoprotein substrate Non-substrate 0.6708
P-glycoprotein inhibitor I Non-inhibitor 0.8881
P-glycoprotein inhibitor II Non-inhibitor 0.9638
Renal organic cation transporter Non-inhibitor 0.9514
CYP450 2C9 substrate Non-substrate 0.7392
CYP450 2D6 substrate Non-substrate 0.8296
CYP450 3A4 substrate Non-substrate 0.6194
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8807
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8276
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.587
Biodegradation Not ready biodegradable 0.9949
Rat acute toxicity 2.2873 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.846
hERG inhibition (predictor II) Non-inhibitor 0.8701
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
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Betapace AF 100 160 mg tablet Box538.2USDbox
Betapace AF 60 120 mg tablet Bottle311.06USDbottle
Betapace 240 mg tablet8.94USDtablet
Sotalol hcl 150 mg/10 ml vial7.8USDml
Betapace 160 mg tablet6.87USDtablet
Betapace af 160 mg tablet6.24USDtablet
Sorine 240 mg tablet5.6USDtablet
Betapace 120 mg tablet5.5USDtablet
Sotalol HCl 240 mg tablet5.29USDtablet
Sotalol 240 mg tablet5.09USDtablet
Betapace af 120 mg tablet4.99USDtablet
Sotalol HCl (AF) 160 mg tablet4.45USDtablet
Sorine 160 mg tablet4.31USDtablet
Sotalol af 160 mg tablet4.27USDtablet
Betapace 80 mg tablet4.12USDtablet
Sotalol HCl 160 mg tablet4.07USDtablet
Sotalol 160 mg tablet3.92USDtablet
Betapace af 80 mg tablet3.74USDtablet
Sotalol HCl (AF) 120 mg tablet3.56USDtablet
Sorine 120 mg tablet3.46USDtablet
Sotalol af 120 mg tablet3.42USDtablet
Sotalol HCl 120 mg tablet3.26USDtablet
Sotalol 120 mg tablet3.13USDtablet
Sotalol HCl 80 mg tablet2.67USDtablet
Sotalol HCl (AF) 80 mg tablet2.67USDtablet
Sorine 80 mg tablet2.61USDtablet
Sotalol af 80 mg tablet2.56USDtablet
Sotalol 80 mg tablet2.35USDtablet
Apo-Sotalol 160 mg Tablet0.68USDtablet
Co Sotalol 160 mg Tablet0.68USDtablet
Mylan-Sotalol 160 mg Tablet0.68USDtablet
Novo-Sotalol 160 mg Tablet0.68USDtablet
Nu-Sotalol 160 mg Tablet0.68USDtablet
Pms-Sotalol 160 mg Tablet0.68USDtablet
Ratio-Sotalol 160 mg Tablet0.68USDtablet
Sandoz Sotalol 160 mg Tablet0.68USDtablet
Apo-Sotalol 80 mg Tablet0.62USDtablet
Co Sotalol 80 mg Tablet0.62USDtablet
Mylan-Sotalol 80 mg Tablet0.62USDtablet
Novo-Sotalol 80 mg Tablet0.62USDtablet
Nu-Sotalol 80 mg Tablet0.62USDtablet
Pms-Sotalol 80 mg Tablet0.62USDtablet
Ratio-Sotalol 80 mg Tablet0.62USDtablet
Sandoz Sotalol 80 mg Tablet0.62USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point206.5-207 °CPhysProp
water solubilitySoluble (5510 mg/L)Not Available
logP0.24BURGOT,G ET AL. (1990)
Predicted Properties
PropertyValueSource
water solubility7.82e-01 g/lALOGPS
logP0.85ALOGPS
logP-0.4ChemAxon
logS-2.5ALOGPS
pKa (strongest acidic)10.07ChemAxon
pKa (strongest basic)9.43ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area78.43ChemAxon
rotatable bond count5ChemAxon
refractivity71.12ChemAxon
polarizability29.34ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG CompoundC07309
PubChem Compound5253
PubChem Substance46505012
ChemSpider5063
BindingDB25762
Therapeutic Targets DatabaseDAP000372
PharmGKBPA451457
Drug Product Database2257858
RxListhttp://www.rxlist.com/cgi/generic/betapaceaf.htm
Drugs.comhttp://www.drugs.com/cdi/sotalol.html
WikipediaSotalol
ATC CodesC07AA07C07AA57
AHFS Codes
  • 24:24.00
PDB EntriesNot Available
FDA labelshow(93.8 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetohexamideThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
AminophyllineAntagonism of action and increased effect of theophylline
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ChlorpropamideThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
CisaprideIncreased risk of cardiotoxicity and arrhythmias
ClarithromycinIncreased risk of cardiotoxicity and arrhythmias
ClonidineIncreased hypertension when clonidine stopped
DihydroergotamineIschemia with risk of gangrene
DisopyramideThe beta-blocker, sotalol, may increase the toxicity of disopyramide.
EpinephrineHypertension, then bradycardia
ErgotamineIschemia with risk of gangrene
ErythromycinIncreased risk of cardiotoxicity and arrhythmias
FenoterolAntagonism
FingolimodPharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
FormoterolAntagonism
GatifloxacinIncreased risk of cardiotoxicity and arrhythmias
GliclazideThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
GlyburideThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
IbuprofenRisk of inhibition of renal prostaglandins
IndomethacinRisk of inhibition of renal prostaglandins
Insulin GlargineThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
LevofloxacinIncreased risk of cardiotoxicity and arrhythmias
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MethyldopaPossible hypertensive crisis
MethysergideIschemia with risk of gangrene
MoxifloxacinIncreased risk of cardiotoxicity and arrhythmias
OrciprenalineAntagonism
OxtriphyllineAntagonism of action and increased effect of theophylline
PipobromanAntagonism
PiroxicamRisk of inhibition of renal prostaglandins
PrazosinRisk of hypotension at the beginning of therapy
RanolazinePossible additive effect on QT prolongation
RepaglinideThe beta-blocker, sotalol, may decrease symptoms of hypoglycemia.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
TelithromycinAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TerbutalineAntagonism
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TheophyllineAntagonism of action and increased effect of theophylline
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
ToremifeneAdditive 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.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol decanoateAdditive 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 InteractionsNot Available

Targets

1. Potassium voltage-gated channel subfamily H member 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Potassium voltage-gated channel subfamily H member 2 Q12809 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-1 adrenergic receptor P08588 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Beta-2 adrenergic receptor P07550 Details

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

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Drug created on June 13, 2005 07:24 / Updated on February 21, 2014 12:54