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Identification
- Summary
Dronedarone is an antiarrhythmic agent used in the reduce the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation.
- Brand Names
- Multaq
- Generic Name
- Dronedarone
- DrugBank Accession Number
- DB04855
- Background
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
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dronedarone (DB04855)
- Weight
- Average: 556.756
Monoisotopic: 556.297093218 - Chemical Formula
- C31H44N2O5S
- 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
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
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Atrial fibrillation •••••••••••• •••••••••• •••••• •••••••••••• •••••• Management of Atrial fibrillation •••••••••••• •••••••••• •••••• •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
- 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
Hover over products below to view reaction partners
- 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
- Adverse Effects
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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
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Dronedarone. Abametapir The serum concentration of Dronedarone can be increased when it is combined with Abametapir. Abatacept The metabolism of Dronedarone can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Dronedarone. Abiraterone The metabolism of Abiraterone can be decreased when combined with Dronedarone. - Food Interactions
- Avoid grapefruit products. Co-administration with grapefruit may increase drug concentrations by 3-fold.
- Avoid St. John's Wort. This herb induces CYP3A4 and may increase the serum concentration of dronedarone.
- Take with food. Food, especially high-fat food, increases drug absorption.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Dronedarone hydrochloride FA36DV299Q 141625-93-6 DWKVCQXJYURSIQ-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Asn-dronedarone Tablet 400 mg Oral Ascend Laboratories Ltd Not applicable Not applicable Canada 
Multaq Tablet, film coated 400 mg Oral SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU 
Multaq Tablet 400 mg Oral Sanofi Aventis 2009-09-28 Not applicable Canada Multaq Tablet, film coated 400 mg/1 Oral Physicians Total Care, Inc. 2010-02-23 Not applicable US 
Multaq Tablet, film coated 400 mg Oral SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU
Categories
- ATC Codes
- C01BD07 — Dronedarone
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Antiarrhythmic agents
- Antiarrhythmics, Class III
- Benzofurans
- Bradycardia-Causing Agents
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs causing inadvertant photosensitivity
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- Narrow Therapeutic Index Drugs
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OCT1 inhibitors
- OCT2 Inhibitors
- P-glycoprotein inhibitors
- Photosensitizing Agents
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 3-aroylfuran / Alkyl aryl ether / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl-phenylketone / Benzenoid / Benzofuran / Benzoyl / Ether show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, aromatic ether, sulfonamide, 1-benzofurans, aromatic ketone (CHEBI:50659)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- JQZ1L091Y2
- CAS number
- 141626-36-0
- 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
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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 21. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 257). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- MULTAQ® (dronedarone hydrochloride) Product Monograph [Link]
- MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health [Link]
- Health Canada Endorsed Important Safety Information on Multaq [Link]
- Atrial Fibrillation (A Fib) - StatPearls - NCBI Bookshelf [Link]
- FDA Approved Drug Products: Multaq (dronedarone) oral tablets [Link]
- FDA Approved Drug Products: Multaq (dronedarone) tablets for oral use (October 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0251621
- KEGG Drug
- D02537
- PubChem Compound
- 208898
- PubChem Substance
- 175426865
- ChemSpider
- 180996
- BindingDB
- 50151864
- 233698
- ChEBI
- 50659
- ChEMBL
- CHEMBL184412
- ZINC
- ZINC000049933061
- PharmGKB
- PA153619853
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dronedarone
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Treatment Atrial Fibrillation 1 somestatus stop reason just information to hide Not Available Completed Not Available Atrial Fibrillation 1 somestatus stop reason just information to hide Not Available Completed Treatment Atrial Fibrillation 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Arrhythmia / Persistent Atrial Fibrillation (AF) 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Persistent Atrial Fibrillation (AF) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 400 mg Tablet, film coated Oral 400 mg/1 Tablet, coated Oral 400 mg Tablet, film coated Oral 400 mg Tablet Oral 426.000 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2294812 No 2009-09-29 2018-06-19 Canada CA2047773 No 2000-09-12 2011-07-24 Canada US5223510 No 1993-06-29 2016-07-26 US US8410167 No 2013-04-02 2029-04-16 US US8602215 No 2013-12-10 2031-06-30 US US9107900 No 2015-08-18 2029-04-16 US US8318800 No 2012-11-27 2018-06-19 US US7323493 No 2008-01-29 2018-06-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 137-145 MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health water solubility 0.64 g/l MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health logP 4.63 MULTAQ® (dronedarone) Safety Data Sheet - Van Wert Health - Predicted Properties
Property Value Source Water Solubility 0.00201 mg/mL ALOGPS logP 6.46 ALOGPS logP 5.18 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 9.18 Chemaxon pKa (Strongest Basic) 10.31 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 88.85 Å2 Chemaxon Rotatable Bond Count 17 Chemaxon Refractivity 158.13 m3·mol-1 Chemaxon Polarizability 66.05 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9156 Caco-2 permeable - 0.6057 P-glycoprotein substrate Substrate 0.6265 P-glycoprotein inhibitor I Inhibitor 0.7879 P-glycoprotein inhibitor II Non-inhibitor 0.5218 Renal organic cation transporter Non-inhibitor 0.7334 CYP450 2C9 substrate Non-substrate 0.7339 CYP450 2D6 substrate Non-substrate 0.7682 CYP450 3A4 substrate Substrate 0.6963 CYP450 1A2 substrate Non-inhibitor 0.5487 CYP450 2C9 inhibitor Inhibitor 0.6209 CYP450 2D6 inhibitor Non-inhibitor 0.8299 CYP450 2C19 inhibitor Non-inhibitor 0.5319 CYP450 3A4 inhibitor Non-inhibitor 0.5198 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8288 Ames test Non AMES toxic 0.5248 Carcinogenicity Non-carcinogens 0.6132 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6273 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.8036 hERG inhibition (predictor II) Inhibitor 0.8051
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 245.1934713 predictedDarkChem Lite v0.1.0 [M-H]- 228.9139 predictedDeepCCS 1.0 (2019) [M+H]+ 244.7341713 predictedDarkChem Lite v0.1.0 [M+H]+ 231.30943 predictedDeepCCS 1.0 (2019) [M+Na]+ 245.2514713 predictedDarkChem Lite v0.1.0 [M+Na]+ 237.22197 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Blocker
- General Function
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:12130714, PubMed:8505626). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets
- Specific Function
- alpha-actinin binding
- Gene Name
- KCNA5
- Uniprot ID
- P22460
- Uniprot Name
- Potassium voltage-gated channel subfamily A member 5
- Molecular Weight
- 67227.15 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
- Specific Function
- alpha1-adrenergic receptor activity
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
- Specific Function
- alpha-1B adrenergic receptor binding
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 50646.17 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol
- Specific Function
- alpha2-adrenergic receptor activity
- Gene Name
- ADRA2B
- Uniprot ID
- P18089
- Uniprot Name
- Alpha-2B adrenergic receptor
- Molecular Weight
- 49953.145 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins
- Specific Function
- alpha-2A adrenergic receptor binding
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661)
- Specific Function
- C3HC4-type RING finger domain binding
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- alpha-actinin binding
- Gene Name
- CACNA1C
- Uniprot ID
- Q13936
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1C
- Molecular Weight
- 248974.1 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines
- Specific Function
- alpha-actinin binding
- Gene Name
- CACNA1D
- Uniprot ID
- Q01668
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1D
- Molecular Weight
- 245138.75 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines. Activates at more negative voltages and does not undergo calcium-dependent inactivation (CDI), due to incoming calcium ions, during depolarization
- Specific Function
- high voltage-gated calcium channel activity
- Gene Name
- CACNA1F
- Uniprot ID
- O60840
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1F
- Molecular Weight
- 220675.9 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group
- Specific Function
- calmodulin binding
- Gene Name
- CACNA1S
- Uniprot ID
- Q13698
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1S
- Molecular Weight
- 212348.1 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Regulatory subunit of L-type calcium channels (PubMed:1309651, PubMed:15615847, PubMed:8107964). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane (PubMed:15615847). Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit (PubMed:1309651). Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (PubMed:8107964)
- Specific Function
- high voltage-gated calcium channel activity
- Gene Name
- CACNB1
- Uniprot ID
- Q02641
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-1
- Molecular Weight
- 65712.995 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370)
- Specific Function
- actin filament binding
- Gene Name
- CACNB2
- Uniprot ID
- Q08289
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-2
- Molecular Weight
- 73579.925 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:8119293). Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity)
- Specific Function
- calcium channel regulator activity
- Gene Name
- CACNB3
- Uniprot ID
- P54284
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-3
- Molecular Weight
- 54531.425 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
- Specific Function
- protein kinase binding
- Gene Name
- CACNB4
- Uniprot ID
- O00305
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-4
- Molecular Weight
- 58168.625 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2. In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity)
- Specific Function
- outward rectifier potassium channel activity
- Gene Name
- KCNK2
- Uniprot ID
- O95069
- Uniprot Name
- Potassium channel subfamily K member 2
- Molecular Weight
- 47092.215 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity)
- Specific Function
- ankyrin binding
- Gene Name
- SCN5A
- Uniprot ID
- Q14524
- Uniprot Name
- Sodium channel protein type 5 subunit alpha
- Molecular Weight
- 226937.475 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat
- Specific Function
- G-protein activated inward rectifier potassium channel activity
- Gene Name
- KCNJ3
- Uniprot ID
- P48549
- Uniprot Name
- G protein-activated inward rectifier potassium channel 1
- Molecular Weight
- 56602.84 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability
- Specific Function
- calmodulin binding
- Gene Name
- KCNQ1
- Uniprot ID
- P51787
- Uniprot Name
- Potassium voltage-gated channel subfamily KQT member 1
- Molecular Weight
- 74697.925 Da
References
- 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. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium
- Specific Function
- inward rectifier potassium channel activity
Components:
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 cellular processes (PubMed:11241183, PubMed:1374913, PubMed:1476165). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:11241183, PubMed:1374913, PubMed:1476165). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum (PubMed:11241183, PubMed:1374913, PubMed:1476165). SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:11241183, PubMed:1374913, PubMed:1476165). Required for normal embryonic heart development and the onset of heart contractions (By similarity)
- Specific Function
- ankyrin binding
- Gene Name
- SLC8A1
- Uniprot ID
- P32418
- Uniprot Name
- Sodium/calcium exchanger 1
- Molecular Weight
- 108546.06 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220)
- Specific Function
- A-type (transient outward) potassium channel activity
- Gene Name
- KCND3
- Uniprot ID
- Q9UK17
- Uniprot Name
- A-type voltage-gated potassium channel KCND3
- Molecular Weight
- 73450.53 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General 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 equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062)
- Specific Function
- alpha-2A adrenergic receptor binding
- Gene Name
- ADRB1
- Uniprot ID
- P08588
- Uniprot Name
- Beta-1 adrenergic receptor
- Molecular Weight
- 51222.97 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine
- Specific Function
- chromatin DNA binding
- Gene Name
- THRA
- Uniprot ID
- P10827
- Uniprot Name
- Thyroid hormone receptor alpha
- Molecular Weight
- 54815.055 Da
References
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Dronedarone FDA Label [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- MULTAQ® (dronedarone hydrochloride) Product Monograph [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- acetylcholine transmembrane transporter activity
- 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
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- 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
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- 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
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- 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
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
Drug created at October 18, 2007 23:47 / Updated at October 07, 2024 13:57