Identification

Name
Dronedarone
Accession Number
DB04855
Type
Small Molecule
Groups
Approved
Description

Dronedarone is a sinus rhythm controller for management of paroxysmal or persistent atrial fibrillation. Classified as a Class III antiarrhythmic but displays properties of all four Vaughan-Williams classes, dronedarone blocks a multitude of channels (sodium, potassium, calcium), and demonstrates antiadrenergic properties. Chemically, it is a benzofuran derivative. FDA approved on July 1, 2009.

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
  • SR 33589
  • SR 33589b
External IDs
SR-33589 / SR33589
Product Ingredients
IngredientUNIICASInChI Key
Dronedarone HydrochlorideFA36DV299Q141625-93-6DWKVCQXJYURSIQ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MultaqTablet400 mgOralSanofi Aventis2009-09-28Not applicableCanada
MultaqTablet, film coated400 mg/1OralCardinal Health2009-07-01Not applicableUs
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
MultaqTablet, film coated400 mgOralSanofi Aventis Groupe2009-11-26Not applicableEu
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
International/Other Brands
Multaq
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

Management of paroxysmal or persistent atrial fibrillation via restoration of normal sinus rhythm.

Associated Conditions
Pharmacodynamics

Dronedarone is a non-iodinated benzofuran derivative for the management of paroxysmal or persistent atrial fibrillation. Dronedarone inhibits human atrial sodium currents (INa) in a dose dependent manner in which a concentration of 0.3 μM is sufficient to completely inhibit INa. Chemically it is related to amiodarone, a popular antiarrhythmic the use of which is limited to toxicity due its high iodine content (pulmonary fibrosis, thyroid disease) as well as by liver disease. Dronedarone lacks the iodine, and is expected to have less toxicity, yet it displays amiodarone-like class III antiarrhytmic activity in vitro and in clinical trials. Despite this advantage over amiodarone, clinical trials of dronedarone have shown that it may increase risk of stroke and mortality from cardiovascular causes and arrhythmia. Furthermore, amiodarone more potently effects action potential and refractory periods than dronedarone.

Mechanism of action

The antiarrhythmic effect of dronedarone may be due to at least two major actions. It prolongs the duration of action potential and refractory period in myocardial tissue via inhibition of sodium and potassium channels. Via inhibition of calcium channels and blockage of beta1-adrenergic receptors, a decrease in AV conduction and sinus node function can be observed. Dronedarone can also cause an increase in blood pressure by inhibition of alpha1-adrenergic receptors.

TargetActionsOrganism
UAlpha-1A adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-1D adrenergic receptorNot AvailableHuman
UAlpha-2A adrenergic receptorNot AvailableHuman
UAlpha-2B adrenergic receptorNot AvailableHuman
UAlpha-2C adrenergic receptorNot AvailableHuman
UBeta-1 adrenergic receptorNot AvailableHuman
UPotassium voltage-gated channel subfamily H member 2Not AvailableHuman
UVoltage-dependent L-type calcium channel subunit alpha-1CNot AvailableHuman
UVoltage-dependent L-type calcium channel subunit alpha-1DNot AvailableHuman
UVoltage-dependent L-type calcium channel subunit alpha-1FNot AvailableHuman
UVoltage-dependent L-type calcium channel subunit alpha-1SNot AvailableHuman
UVoltage-dependent L-type calcium channel subunit beta-1Not AvailableHuman
UVoltage-dependent L-type calcium channel subunit beta-2Not AvailableHuman
UVoltage-dependent L-type calcium channel subunit beta-3Not AvailableHuman
UVoltage-dependent L-type calcium channel subunit beta-4Not AvailableHuman
USodium channel protein type 1 subunit alpha
inhibitor
Human
UPotassium channel subfamily K member 2
inhibitor
Human
Absorption

Because of presystemic first pass metabolism the absolute bioavailability of dronedarone without food is low, about 4%. It increases to approximately 15% when dronedarone is administered with a high fat meal. After oral administration in fed conditions, peak plasma concentrations of dronedarone and the main circulating active metabolite (N-debutyl metabolite) are reached within 3 to 6 hours. After repeated administration of 400 mg twice daily, steady state is reached within 4 to 8 days of treatment. The steady state Cmax and exposure of the main N-debutyl metabolite is similar to that of the parent compound.

Volume of distribution

When intravenously administered, the volume of distribution is 1400 L.

Protein binding

Dronedarone and its N-debutyl metabolite is >98% protein bound - mainly to albumin.

Metabolism

Majority of dronedarone is eliminated by first-pass metabolism in the liver by CYP3A4 enzymes (>84%). Dronedarone is also metabolized by CYP2D6 to a lesser extent. N-DBD is its active metabolite (1/10 to 1/3 potency of dronedarone) which can penetrate the blood-brain barrier, placenta, and is excreted in breast milk. However, it does not significantly accumulate in plasma or tissue.

Route of elimination

6% of the dose was excreted in the urine, mainly as metabolites (no unchanged compound excreted in urine), and 84% was excreted in feces, mainly as metabolites.

Half life

Elimination half-life: 13-19 hours

Clearance

Plasma clearance = 130-150 L/h.

Toxicity

Most common adverse reactions (≥2%) are diarrhea, nausea, abdominal pain, vomiting, and asthenia.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Dronedarone can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Dronedarone can be decreased when combined with (S)-Warfarin.
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 risk or severity of hypertension can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Dronedarone.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Dronedarone is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when 3,4-Methylenedioxyamphetamine is combined with Dronedarone.
3,5-diiodothyropropionic acidThe metabolism of Dronedarone can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Dronedarone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Dronedarone.
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. 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. 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]
  3. Celestino D, Medei E, Moro S, Elizari MV, Sicouri S: Acute in vitro effects of dronedarone, an iodine-free derivative, and amiodarone, on the rabbit sinoatrial node automaticity: a comparative study. J Cardiovasc Pharmacol Ther. 2007 Sep;12(3):248-57. [PubMed:17875953]
  4. Pamukcu B, Lip GY: Dronedarone as a new treatment option for atrial fibrillation patients: pharmacokinetics, pharmacodynamics and clinical practice. Expert Opin Pharmacother. 2011 Jan;12(1):131-40. doi: 10.1517/14656566.2011.540800. Epub 2010 Dec 2. [PubMed:21126199]
  5. 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]
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
FDA label
Download (606 KB)
MSDS
Download (115 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNonvalvular Atrial Fibrillation1
3CompletedPreventionAtrial Flutter / Nonvalvular Atrial Fibrillation1
3CompletedPreventionNonvalvular Atrial Fibrillation1
3CompletedTreatmentAtrial Flutter / Nonvalvular Atrial Fibrillation2
3CompletedTreatmentNonvalvular Atrial Fibrillation2
3TerminatedTreatmentCongestive Heart Failure (CHF)1
3TerminatedTreatmentNonvalvular Atrial Fibrillation1
4CompletedTreatmentNonvalvular Atrial Fibrillation3
4TerminatedTreatmentNonvalvular Atrial Fibrillation3
4Unknown StatusTreatmentParoxysmal Atrial Fibrillation (PAF)1
Not AvailableActive Not RecruitingTreatmentNonvalvular Atrial Fibrillation / Quality of Life1
Not AvailableCompletedTreatmentNonvalvular Atrial Fibrillation1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableUnknown StatusTreatmentDronedarone / ICD Shocks / ICDs1
Not AvailableUnknown StatusTreatmentNonvalvular Atrial Fibrillation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral400 mg
Tablet, film coatedOral400 mg
Tablet, film coatedOral400 mg/1
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

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
logP7.346MSDS
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
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
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 protein forms a...
Gene Name
SCN1A
Uniprot ID
P35498
Uniprot Name
Sodium channel protein type 1 subunit alpha
Molecular Weight
228969.49 Da
References
  1. 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
Human
Pharmacological action
Unknown
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]

Enzymes

Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]

Drug created on October 18, 2007 17:47 / Updated on December 18, 2018 05:46