Identification

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Name
Dronedarone
Accession Number
DB04855
Type
Small Molecule
Groups
Approved
Description

Dronedarone is a Class III antiarrhythmic drug that works to restore the normal sinus rhythm in patients with paroxysmal or persistent atrial fibrillation. Atrial fibrillation is a common sustained arrhythmia where the treatment primarily focuses on stroke prevention and symptom management. It is managed by rate control, rhythm control, prevention of thromboembolic events, and treatment of the underlying disease.1 Similar to amiodarone, dronedarone is a multichannel blocker that works to control rhythm and rate in atrial fibrillation.2 It meets criteria of all four Vaughan Williams antiarrhythmic drug classes by blocking sodium, potassium, and calcium ion channels and inhibiting β-adrenergic receptors.1,13

Dronedarone is a related benzofuran compound to amiodarone but its chemical structure lacks iodine moieties which are associated with amiodarone-induced thyroid problems.1,8 Additionally, the methyl sulfonyl group in its structure renders dronedarone to be more lipophilic with a shorter half-life than amiodarone.1 This ultimately leads to reduced tissue accumulation of the drug and decreased risk for organ toxicities, such as thyroid and pulmonary toxicities.8 Commonly marketed as Multaq®, dronedarone was approved by the FDA in July 2009 and Health Canada in August 2009. A safety concern for the risk of drug-induced hepatocellular injury has been issued following marketing of dronedarone.11

Structure
Thumb
Synonyms
  • Dronedarona
  • Dronedarone
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)-methanesulfonamide
  • N-(2-butyl-3-(p-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide
External IDs
SR 33589 / SR-33589 / SR33589
Product Ingredients
IngredientUNIICASInChI Key
Dronedarone hydrochlorideFA36DV299Q141625-93-6DWKVCQXJYURSIQ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
MultaqTablet, film coated400 mg/1Oralsanofi-aventis U.S. LLC2009-07-01Not applicableUs
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
MultaqTablet, film coated400 mg/1OralPhysicians Total Care, Inc.2010-02-23Not applicableUs
MultaqTablet400 mgOralSanofi Aventis2009-09-28Not applicableCanada
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
MultaqTablet, film coated400 mg/1OralCardinal Health2009-07-01Not applicableUs
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
JQZ1L091Y2
CAS number
141626-36-0
Weight
Average: 556.756
Monoisotopic: 556.297093218
Chemical Formula
C31H44N2O5S
InChI Key
ZQTNQVWKHCQYLQ-UHFFFAOYSA-N
InChI
InChI=1S/C31H44N2O5S/c1-5-8-12-29-30(27-23-25(32-39(4,35)36)15-18-28(27)38-29)31(34)24-13-16-26(17-14-24)37-22-11-21-33(19-9-6-2)20-10-7-3/h13-18,23,32H,5-12,19-22H2,1-4H3
IUPAC Name
N-(2-butyl-3-{4-[3-(dibutylamino)propoxy]benzoyl}-1-benzofuran-5-yl)methanesulfonamide
SMILES
CCCCN(CCCC)CCCOC1=CC=C(C=C1)C(=O)C1=C(CCCC)OC2=C1C=C(NS(C)(=O)=O)C=C2

Pharmacology

Indication

Dronedarone is indicated for the management of atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF to reduce the risk of hospitalization.13

Associated Conditions
Pharmacodynamics

Dronedarone is an antiarrhythmic agent that restores normal sinus rhythm and reduces heart rate in atrial fibrillation. In another model, it prevents ventricular tachycardia and ventricular fibrillation.9 Dronedarone moderately prolongs the QTc interval by about 10 ms on average.13 Dronedarone decreases arterial blood pressure and reduces oxygen consumption. It reduces myocardial contractility with no change in left ventricular ejection fraction. Dronedarone vasodilates coronary arteries through activation of the nitric oxide pathway.9 In clinical studies, dronedarone reduced incidence of hospitalizations for acute coronary syndromes and reduced incidence of stroke.3 Dronedarone exhibits antiadrenergic effects by reducing alpha-adrenergic blood pressure response to epinephrine and beta 1 and beta 2 responses to isoproterenol.9

Dronedarone was shown to inhibit triiodothyronine (T3) signalling by binding to TRα1 but much less so to TRβ1.7 The treatment of dronedarone in patients with severe heart failure and left ventricular systolic dysfunction was associated with increased early mortality related to the worsening of heart failure.4 In animal studies, the use of dronedarone at doses equivalent to the recommended human doses was associated with fetal harm. In clinical studies and postmarketing reports, dronedarone was shown to cause hepatocellular liver injury and pulmonary toxicities, such as interstitial lung disease, pneumonitis, and pulmonary fibrosis.13 Compared to its related compound amiodarone, dronedarone has a faster onset and offset of actions with a shorter elimination half-life and low tissue accumulation.1,8

Mechanism of action

Atrial fibrillation is the most common type of arrhythmia that is caused by abnormal electrical activity in the atria. In atrial fibrillation, tachyarrhythmia, or fast heart rate, can either be paroxysmal (less than 7 days) or persistent (more than 7 days). Atrial fibrillation causes turbulent and abnormal blood flow through the heart chambers, leading to decreased the effectiveness of the heart to pump blood and an increased likelihood of thrombus formation within the atria which can ultimately dislodge and cause a stroke.12

Dronedarone achieves heart rate and rhythm control in atrial fibrillation. In vitro, dronedarone decreased the maximum rate of the rise of an action potential in a concentration- and frequency-dependent manner.2 Cardiac action potentials are generated by ionic currents of multiple voltage-gated ion channels, including potassium, sodium, and calcium channels.6 Dronedarone is a multichannel blocker that meets the criteria of all four Vaughan Williams antiarrhythmic drug classes1 but the contribution of each of these activities to the drug's antiarrhythmic effect is unknown.13 Dronedarone inhibits rapid Na+ currents rate-dependently (class Ib), non-competitively antagonizes α– and β-adrenergic receptors (class II), blocks K+ outward currents (class III) and blocks slow Ca2+ inward currents (class IV).1 More specifically, it decreases delayed-rectifier K+ current (IKr), slowly activating delayed-rectifier K+ current (IKs), inward rectifier potassium current (IK1), peak Na+ current (INa) and L-type Ca2+ current (ICa (L)).2,3 Dronedarone ultimately increases refractory periods, decelerates cardiac conduction, and prolongs cardiac action potential and refractory periods.1,9

TargetActionsOrganism
AAlpha-1A adrenergic receptor
antagonist
Humans
AAlpha-1B adrenergic receptor
antagonist
Humans
AAlpha-1D adrenergic receptor
antagonist
Humans
AAlpha-2A adrenergic receptor
antagonist
Humans
AAlpha-2B adrenergic receptor
antagonist
Humans
AAlpha-2C adrenergic receptor
antagonist
Humans
UBeta-1 adrenergic receptor
antagonist
Humans
APotassium voltage-gated channel subfamily H member 2
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1D
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1F
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit alpha-1S
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit beta-1
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit beta-2
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit beta-3
inhibitor
Humans
AVoltage-dependent L-type calcium channel subunit beta-4
inhibitor
Humans
APotassium channel subfamily K member 2
inhibitor
Humans
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
AG protein-activated inward rectifier potassium channel 1
inhibitor
Humans
APotassium voltage-gated channel subfamily KQT member 1
inhibitor
Humans
AInward rectifier potassium channel
inhibitor
Humans
ASodium/calcium exchanger 1
inhibitor
Humans
APotassium voltage-gated channel subfamily D member 3
inhibitor
Humans
NThyroid hormone receptor alpha
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Dronedarone is well absorbed after oral administration (>70%).1 It displays low systemic bioavailability due to extensive first-pass metabolism. The absolute bioavailability of dronedarone without and with a high-fat meal is 4% and 15%, respectively. The peak plasma concentrations of dronedarone and its main circulating N-debutyl metabolite are reached within 3 to 6 hours after administration with food.

Following repeated administration of 400 mg dronedarone twice daily, the steady-state was reached within 4 to 8 days of initial treatment. The steady-state Cmax and systemic exposure to the N-debutyl metabolite are similar to that of the parent compound.13

Volume of distribution

The volume of distribution at steady-state ranges from 1200 to 1400 L following intravenous administration.13

Protein binding

The in vitro plasma protein binding of dronedarone and its N-debutyl metabolite is 99.7% and 98.5%, respectively. Both mainly bind to albumin and are not capable of saturation.1

Metabolism

Dronedarone predominantly undergoes CYP3A-mediated hepatic metabolism. Initial metabolism of dronedarone involves N-debutylation to form the N-debutyl-dronedarone, which retains 1/10 to 1/3 of pharmacological activity of the parent compound.13 N-debutyl-dronedarone can be further metabolized to phenol-dronedarone via O-dealkylation and propanoic acid-dronedarone via oxidative deamination. Dronedarone can also be metabolized by CYP2D6 to form benzofuran-hydroxyl-dronedarone. Other detectable metabolites include C-dealkyl-dronedarone and dibutylamine-hydroxyl-dronedarone, along with other minor downstream metabolites with undetermined chemical structures.5

Route of elimination

Following oral administration, about 84% of the labeled dose is excreted in feces and 6% is excreted in urine, mainly as metabolites. Unchanged parent compound and the N-debutyl metabolite accounted for less than 15% of the total radioactivity in the plasma.13

Half life

The elimination half life ranges from 13 to 19 hours.13

Clearance

Following intravenous administration, the clearance ranged from 130 to 150 L/h.13

Toxicity

In an acute toxicity study, the oral LD50 in rat was >2,000 mg/kg.10

In oral studies, dronedarone showed a limited potential for toxicity in humans in acute overdose situations.9 However, it is recommended that the patient's cardiac rhythm and blood pressure is monitored in the event of overdose. Symptomatic and supportive treatments should be initiated.13

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Dronedarone.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Dronedarone.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid is combined with Dronedarone.
1-benzylimidazoleThe risk or severity of hypertension can be increased when 1-benzylimidazole is combined with Dronedarone.
2,5-Dimethoxy-4-ethylamphetamineThe therapeutic efficacy of Dronedarone can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe therapeutic efficacy of Dronedarone can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe therapeutic efficacy of Dronedarone can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamineThe therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Dronedarone.
4-hydroxycoumarinThe serum concentration of Dronedarone can be increased when it is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Dronedarone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Absorption of dronedarone increases 3-fold if taken with food especially if meal is high in fat content
  • Do not take dronedarone with grapefruit juice. Grapefruit juice is a potent CYP3A4 inhibitor which will increase serum concentrations of dronedarone threefold

References

Synthesis Reference

Arie Gutman, Gennadi Nisnevich, Lev Yudovitch, "Process for the preparation of dronedarone." U.S. Patent US20050049302, issued March 03, 2005.

US20050049302
General References
  1. Schweizer PA, Becker R, Katus HA, Thomas D: Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation. Drug Des Devel Ther. 2011 Jan 6;5:27-39. doi: 10.2147/DDDT.S10315. [PubMed:21267357]
  2. Patel PD, Bhuriya R, Patel DD, Arora BL, Singh PP, Arora RR: Dronedarone for atrial fibrillation: a new therapeutic agent. Vasc Health Risk Manag. 2009;5:635-42. doi: 10.2147/vhrm.s6185. Epub 2009 Aug 6. [PubMed:19688104]
  3. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
  4. Kober L, Torp-Pedersen C, McMurray JJ, Gotzsche O, Levy S, Crijns H, Amlie J, Carlsen J: Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008 Jun 19;358(25):2678-87. doi: 10.1056/NEJMoa0800456. [PubMed:18565860]
  5. Klieber S, Arabeyre-Fabre C, Moliner P, Marti E, Mandray M, Ngo R, Ollier C, Brun P, Fabre G: Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drug. Pharmacol Res Perspect. 2014 Jun;2(3):e00044. doi: 10.1002/prp2.44. Epub 2014 Apr 22. [PubMed:25505590]
  6. Rahm AK, Lugenbiel P, Schweizer PA, Katus HA, Thomas D: Role of ion channels in heart failure and channelopathies. Biophys Rev. 2018 Aug;10(4):1097-1106. doi: 10.1007/s12551-018-0442-3. Epub 2018 Jul 17. [PubMed:30019205]
  7. Van Beeren HC, Jong WM, Kaptein E, Visser TJ, Bakker O, Wiersinga WM: Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence. Endocrinology. 2003 Feb;144(2):552-8. doi: 10.1210/en.2002-220604. [PubMed:12538616]
  8. 21. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 257). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  9. MULTAQ® (dronedarone hydrochloride) Product Monograph [Link]
  10. MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health [Link]
  11. Health Canada Endorsed Important Safety Information on Multaq [Link]
  12. Atrial Fibrillation (A Fib) - StatPearls - NCBI Bookshelf [Link]
  13. MULTAQ (dronedarone) Tablets - FDA Label [Link]
External Links
KEGG Drug
D02537
PubChem Compound
208898
PubChem Substance
175426865
ChemSpider
180996
BindingDB
50151864
ChEBI
50659
ChEMBL
CHEMBL184412
PharmGKB
PA153619853
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dronedarone
ATC Codes
C01BD07 — Dronedarone
AHFS Codes
  • 24:04.04.20 — Class III Antiarrythmics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentAtrial Fibrillation (AF)2
2, 3RecruitingPreventionPostoperative Atrial Fibrillation1
3CompletedPreventionAtrial Fibrillation (AF)1
3CompletedPreventionAtrial Fibrillation (AF) / Atrial Flutter1
3CompletedTreatmentAtrial Fibrillation (AF)2
3CompletedTreatmentAtrial Fibrillation (AF) / Atrial Flutter2
3TerminatedTreatmentAtrial Fibrillation (AF)1
3TerminatedTreatmentCongestive Heart Failure1
4CompletedTreatmentAtrial Fibrillation (AF)3
4TerminatedTreatmentAtrial Fibrillation (AF)3
4Unknown StatusTreatmentParoxysmal Atrial Fibrillation (PAF)1
Not AvailableActive Not RecruitingTreatmentAtrial Fibrillation (AF)1
Not AvailableActive Not RecruitingTreatmentAtrial Fibrillation (AF) / Quality of Life1
Not AvailableCompletedTreatmentAtrial Fibrillation (AF)1
Not AvailableUnknown StatusTreatmentAtrial Fibrillation (AF)1
Not AvailableUnknown StatusTreatmentDronedarone / ICD Shocks / ICDs1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral400 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral400 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2294812No2009-09-292018-06-19Canada
CA2047773No2000-09-122011-07-24Canada
US5223510No1993-06-292016-07-26Us
US8410167No2013-04-022029-04-16Us
US8602215No2013-12-102031-06-30Us
US9107900No2015-08-182029-04-16Us
US8318800No2012-11-272018-06-19Us
US7323493No2008-01-292018-06-19Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)137-145MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health
water solubility0.64 g/lMULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health
logP4.63MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health
Predicted Properties
PropertyValueSource
Water Solubility0.00201 mg/mLALOGPS
logP6.46ALOGPS
logP5.28ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)9.08ChemAxon
pKa (Strongest Basic)9.79ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.85 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity158.13 m3·mol-1ChemAxon
Polarizability66.05 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9156
Caco-2 permeable-0.6057
P-glycoprotein substrateSubstrate0.6265
P-glycoprotein inhibitor IInhibitor0.7879
P-glycoprotein inhibitor IINon-inhibitor0.5218
Renal organic cation transporterNon-inhibitor0.7334
CYP450 2C9 substrateNon-substrate0.7339
CYP450 2D6 substrateNon-substrate0.7682
CYP450 3A4 substrateSubstrate0.6963
CYP450 1A2 substrateNon-inhibitor0.5487
CYP450 2C9 inhibitorInhibitor0.6209
CYP450 2D6 inhibitorNon-inhibitor0.8299
CYP450 2C19 inhibitorNon-inhibitor0.5319
CYP450 3A4 inhibitorNon-inhibitor0.5198
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8288
Ames testNon AMES toxic0.5248
CarcinogenicityNon-carcinogens0.6132
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6273 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8036
hERG inhibition (predictor II)Inhibitor0.8051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0000090000-8897a71d0d4436083f2f
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0000090000-0412b5e5e921a14ade8e
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0000090000-77777b7e67d24302cc61
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0000090000-98e3b8bdab6f810350d0
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0009020000-46fc09138b4d4c98f7db
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000090000-5fc376f78fcd143923df
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000090000-a4ea4fac6f54cdcb7cbc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000090000-c3aef714c9268fa971ca
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0100290000-55925fc920832a562317
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052o-0922440000-21a75dc14e4f6eec2a80
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0011920000-b36c2c2ac812fdf862c0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000090000-6af26e1e5383a4521666
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000090000-8a1e04d2d220b7c178b7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udl-1900000000-1526ae7b1c72d66d17f7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zfr-3900000000-5720b31639362bc77d45
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pb9-6900000000-5862d8b2fbe4b55544fd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9800000000-52425d2c67f0ee9e6833
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000090000-91af4261328f04d47762
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000090000-e6261075748cb68a6673
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udl-1900000000-b6ee80d1389866275d10
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zfr-3900000000-79bd8a4d5fb81c2d7697
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0zfr-6900000000-45b09ec3acdb68cc2d94
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9810000000-e53f3747472fb6644b74
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0011920000-32cc8203ba76ec3246f7

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Sulfanilides / Benzofurans / 3-aroylfurans / Benzoyl derivatives / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Organic sulfonamides / Organosulfonamides / Heteroaromatic compounds
show 6 more
Substituents
Aryl-phenylketone / Sulfanilide / Benzofuran / Phenoxy compound / Benzoyl / Phenol ether / 3-aroylfuran / Alkyl aryl ether / Monocyclic benzene moiety / Organic sulfonic acid amide
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, aromatic ether, sulfonamide, 1-benzofurans, aromatic ketone (CHEBI:50659)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
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 e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Dale KM, White CM: Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007 Apr;41(4):599-605. Epub 2007 Mar 27. [PubMed:17389667]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
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 ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Iwamoto T, Watanabe Y, Kita S, Blaustein MP: Na+/Ca2+ exchange inhibitors: a new class of calcium regulators. Cardiovasc Hematol Disord Drug Targets. 2007 Sep;7(3):188-98. [PubMed:17896959]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1D
Uniprot ID
Q01668
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight
245138.75 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1F
Uniprot ID
O60840
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1F
Molecular Weight
220675.9 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1S
Uniprot ID
Q13698
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight
212348.1 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB1
Uniprot ID
Q02641
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-1
Molecular Weight
65712.995 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB2
Uniprot ID
Q08289
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight
73579.925 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB3
Uniprot ID
P54284
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-3
Molecular Weight
54531.425 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB4
Uniprot ID
O00305
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-4
Molecular Weight
58168.625 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Potassium ion leak channel activity
Specific Function
Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward...
Gene Name
KCNK2
Uniprot ID
O95069
Uniprot Name
Potassium channel subfamily K member 2
Molecular Weight
47092.215 Da
References
  1. Schmidt C, Wiedmann F, Schweizer PA, Becker R, Katus HA, Thomas D: Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels. Naunyn Schmiedebergs Arch Pharmacol. 2012 Oct;385(10):1003-16. doi: 10.1007/s00210-012-0780-9. Epub 2012 Jul 13. [PubMed:22790794]
  2. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
  2. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S: Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol. 2003 Aug;14(8):885-90. [PubMed:12890054]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
G-protein activated inward rectifier potassium channel activity
Specific Function
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their...
Gene Name
KCNJ3
Uniprot ID
P48549
Uniprot Name
G protein-activated inward rectifier potassium channel 1
Molecular Weight
56602.84 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:10646604). Associates with KCNE beta subunits that modul...
Gene Name
KCNQ1
Uniprot ID
P51787
Uniprot Name
Potassium voltage-gated channel subfamily KQT member 1
Molecular Weight
74697.925 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Inward rectifier potassium channel activity
Specific Function
Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable...

Components:
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ion channel binding
Specific Function
Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellul...
Gene Name
SLC8A1
Uniprot ID
P32418
Uniprot Name
Sodium/calcium exchanger 1
Molecular Weight
108546.06 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated...
Gene Name
KCND3
Uniprot ID
Q9UK17
Uniprot Name
Potassium voltage-gated channel subfamily D member 3
Molecular Weight
73450.53 Da
References
  1. Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013. [PubMed:23997577]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Al...
Gene Name
THRA
Uniprot ID
P10827
Uniprot Name
Thyroid hormone receptor alpha
Molecular Weight
54815.055 Da
References
  1. Van Beeren HC, Jong WM, Kaptein E, Visser TJ, Bakker O, Wiersinga WM: Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence. Endocrinology. 2003 Feb;144(2):552-8. doi: 10.1210/en.2002-220604. [PubMed:12538616]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Dorian P: Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation. J Cardiovasc Pharmacol Ther. 2010 Dec;15(4 Suppl):15S-8S. doi: 10.1177/1074248410367792. Epub 2010 May 14. [PubMed:20472816]
  2. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258]
  3. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. Dronedarone FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258]
  2. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242]
  3. Kim MS, Baek IH: Effect of dronedarone on the pharmacokinetics of carvedilol following oral administration to rats. Eur J Pharm Sci. 2018 Jan 1;111:13-19. doi: 10.1016/j.ejps.2017.09.029. Epub 2017 Sep 20. [PubMed:28942006]
  4. Klieber S, Arabeyre-Fabre C, Moliner P, Marti E, Mandray M, Ngo R, Ollier C, Brun P, Fabre G: Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drug. Pharmacol Res Perspect. 2014 Jun;2(3):e00044. doi: 10.1002/prp2.44. Epub 2014 Apr 22. [PubMed:25505590]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Klieber S, Arabeyre-Fabre C, Moliner P, Marti E, Mandray M, Ngo R, Ollier C, Brun P, Fabre G: Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drug. Pharmacol Res Perspect. 2014 Jun;2(3):e00044. doi: 10.1002/prp2.44. Epub 2014 Apr 22. [PubMed:25505590]
  2. Hong Y, Chia YM, Yeo RH, Venkatesan G, Koh SK, Chai CL, Zhou L, Kojodjojo P, Chan EC: Inactivation of Human Cytochrome P450 3A4 and 3A5 by Dronedarone and N-Desbutyl Dronedarone. Mol Pharmacol. 2016 Jan;89(1):1-13. doi: 10.1124/mol.115.100891. Epub 2015 Oct 21. [PubMed:26490246]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
Molecular Weight
57610.165 Da
References
  1. Karkhanis A, Lam HY, Venkatesan G, Koh SK, Chai CL, Zhou L, Hong Y, Kojodjojo P, Chan EC: Multiple modes of inhibition of human cytochrome P450 2J2 by dronedarone, amiodarone and their active metabolites. Biochem Pharmacol. 2016 May 1;107:67-80. doi: 10.1016/j.bcp.2016.03.005. Epub 2016 Mar 10. [PubMed:26972388]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. MULTAQ® (dronedarone hydrochloride) Product Monograph [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. De Ferrari GM, Dusi V: Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf. 2012 Nov;11(6):1023-45. doi: 10.1517/14740338.2012.722994. Epub 2012 Sep 13. [PubMed:22971242]
  2. Schafer JA, Kjesbo NK, Gleason PP: Dronedarone: current evidence and future questions. Cardiovasc Ther. 2010 Spring;28(1):38-47. doi: 10.1111/j.1755-5922.2009.00112.x. [PubMed:20074258]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da

Drug created on October 18, 2007 17:47 / Updated on December 08, 2019 20:10