DT-Web

DB00489 - Sotalol


Identification
Name Sotalol
Accession Number DB00489 (APRD01230)
Type small molecule
Description An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 272.364
Groups approved
Monoisotopic Weight 272.119463206
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.
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 ?1-adrenergic receptors within the myocardium and ?2-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.
Protein binding Sotalol does not bind to plasma proteins.
Biotransformation 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.
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
Interactions
Drug Interactions
Drug Mechanism of 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 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


Potassium voltage-gated channel subfamily H member 2
Name Potassium voltage-gated channel subfamily H member 2
Gene Name KCNH2
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.1893
Beta-1 adrenergic receptor
Name Beta-1 adrenergic receptor
Gene Name ADRB1
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7092
Beta-2 adrenergic receptor
Name Beta-2 adrenergic receptor
Gene Name ADRB2
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.7095

Predictions


Id Partner name Gene Name Score
4119 Cytochrome P450 2D6 CYP2D6 0.1535
1517 Beta-3 adrenergic receptor ADRB3 0.1348
1588 Multidrug resistance protein 1 ABCB1 0.0893
556 Alpha-1A adrenergic receptor ADRA1A 0.0822
4512 Cytochrome P450 3A4 CYP3A4 0.071
320 5-hydroxytryptamine 1A receptor HTR1A 0.0509
4200 Cytochrome P450 1A2 CYP1A2 0.0498
632 Alpha-1B adrenergic receptor ADRA1B 0.0473
6016 Cytochrome P450 2C19 CYP2C19 0.04
6144 Solute carrier family 22 member 2 SLC22A2 0.0376
318 Alpha-2A adrenergic receptor ADRA2A 0.037
789 Alpha-1D adrenergic receptor ADRA1D 0.0369
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.036
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0358
4757 Cytochrome P450 2C9 CYP2C9 0.0313
4118 Cytochrome P450 3A5 CYP3A5 0.0295
233 Potassium channel subfamily K member 2 KCNK2 0.0284
885 5-hydroxytryptamine 1B receptor HTR1B 0.0284
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0281
6024 Cytochrome P450 1A1 CYP1A1 0.028
4924 Cytochrome P450 2C8 CYP2C8 0.028
3923 Cholinesterase BCHE 0.028
6107 Cytochrome P450 3A7 CYP3A7 0.0267
1968 ATP-sensitive inward rectifier potassium channel 12 KCNJ12 0.0252
6145 Solute carrier family 22 member 1 SLC22A1 0.0244
2300 Lysozyme E 0.0243
3633 Lysozyme R 0.0243
5597 Lysozyme 17 0.0243
629 Alpha-2B adrenergic receptor ADRA2B 0.0242
3810 Catechol O-methyltransferase COMT 0.0211
378 Alpha-2C adrenergic receptor ADRA2C 0.0206
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0186
1820 Beta-nerve growth factor NGF 0.0166
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.016
3941 Amine oxidase [flavin-containing] A MAOA 0.0153
4146 Phosphatidylinositol 3-kinase regulatory subunit gamma PIK3R3 0.0151
4145 Phosphatidylinositol 3-kinase regulatory subunit beta PIK3R2 0.0151
828 Phenylalanine-4-hydroxylase PAH 0.0149
3109 Phenylalanine-4-hydroxylase phhA 0.0149
6013 Cytochrome P450 2E1 CYP2E1 0.0147
5718 Cytochrome P450 2A6 CYP2A6 0.0147
6182 Cytochrome P450 2J2 CYP2J2 0.0143
502 5-hydroxytryptamine 2A receptor HTR2A 0.0143
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0133
831 D(2) dopamine receptor DRD2 0.0131
817 DNA topoisomerase 2-alpha TOP2A 0.013
824 Sodium-dependent serotonin transporter SLC6A4 0.0129
1281 Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 0.0125
751 Potassium channel subfamily K member 6 KCNK6 0.0125
4292 Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase lpxA 0.0124
492 Histamine H1 receptor HRH1 0.0122
3076 Antigen 85-C fbpC 0.0122
3086 Plasmepsin-2 Not Available 0.012
1374 Natriuretic peptides B NPPB 0.0117
1827 Gap junction alpha-1 protein GJA1 0.0117
1908 Vascular cell adhesion protein 1 VCAM1 0.0117
172 Potassium channel subfamily K member 1 KCNK1 0.0114
6147 Solute carrier family 22 member 3 SLC22A3 0.0113
777 Tumor necrosis factor TNF 0.0112
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.011
118 Organic cation/carnitine transporter 2 SLC22A5 0.0107
713 Sodium-dependent dopamine transporter SLC6A3 0.0107
23 D(1A) dopamine receptor DRD1 0.0101
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0097
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0095
1256 5-hydroxytryptamine 6 receptor HTR6 0.0094
6847 Lactase-phlorizin hydrolase LCT 0.0093
183 Vascular endothelial growth factor A VEGFA 0.0086
1176 Mitogen-activated protein kinase 1 MAPK1 0.0083
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0082
6030 Cytochrome P450 2B6 CYP2B6 0.0079
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.0074
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0072
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0072
465 Calmodulin CALM1 0.0071
590 5-hydroxytryptamine 2C receptor HTR2C 0.007
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0068
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0067
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0066
638 D(3) dopamine receptor DRD3 0.0066
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0063
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0061
3947 Xanthine dehydrogenase/oxidase XDH 0.006
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0058
131 Synaptic vesicular amine transporter SLC18A2 0.0058
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0056
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0055
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0055
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0055
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0055
833 Organic cation/carnitine transporter 1 SLC22A4 0.0052
94 5-hydroxytryptamine 4 receptor HTR4 0.0051
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0046
20 Prostaglandin G/H synthase 1 PTGS1 0.0046
3939 Amine oxidase [flavin-containing] B MAOB 0.0045
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0041
6151 Monocarboxylate transporter 10 SLC16A10 0.004
341 5-hydroxytryptamine 3 receptor HTR3A 0.0038
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0038
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0038
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0038
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0038
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0038
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0038
1360 Sphingomyelin phosphodiesterase SMPD1 0.0036
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0033
6106 Cytochrome P450 2C18 CYP2C18 0.0032
776 Bile salt export pump ABCB11 0.0031
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0029
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0029
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0028
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0028
124 Histamine H2 receptor HRH2 0.0028
716 5-hydroxytryptamine 7 receptor HTR7 0.0028
6432 Transporter snf 0.0027
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0027
587 Serum albumin ALB 0.0026
436 5-hydroxytryptamine 2B receptor HTR2B 0.0026
432 D(4) dopamine receptor DRD4 0.0025
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0023
260 Cytochrome P450 51 ERG11 0.0023
761 Cytochrome P450 51 ERG11 0.0023
3163 Cytochrome P450 51 cyp51 0.0023
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0022
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0019
7 Nitric oxide synthase, inducible NOS2 0.0019
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0018
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0018
291 Nitric-oxide synthase, endothelial NOS3 0.0018
3811 Cytochrome P450 19A1 CYP19A1 0.0018
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0018
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0017
6142 Solute carrier family 22 member 8 SLC22A8 0.0017
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0016
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0016
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0015
6148 Multidrug resistance-associated protein 7 ABCC10 0.0014
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0013
2164 Multidrug resistance-associated protein 4 ABCC4 0.0012
862 Multidrug resistance-associated protein 1 ABCC1 0.0011
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