| Candidate ID: | R0413 |
| Source ID: | DB01118 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Amiodarone
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| Synonyms: |
2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran; 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone; 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran; Amiodarone
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| Molecular Formula: |
C25H29I2NO3
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| SMILES: |
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2
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| Structure: |
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| DrugBank Description: |
Amiodarone is a benzofuran derivative, anti-arrhythmic drug used commonly in a variety of settings. Most known for its approved indication in life-threatening ventricular arrhythmias, it is also used off-label in the outpatient and inpatient setting for atrial fibrillation. Because of its ability to cause serious toxicity and possibly death, amiodarone use should be reserved for its approved indications, according to prescribing information.
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| CAS Number: |
1951-25-3
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| Molecular Weight: |
645.3116
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| DrugBank Indication: |
The FDA approved indications for amiodarone are recurrent ventricular fibrillation (VF)
and recurrent hemodynamically unstable ventricular tachycardia (VT). The FDA emphasizes that this drug should only be given in these conditions when they are clinically documented and have not responded to normal therapeutic doses of other antiarrhythmic agents, or when other drugs are not tolerated by the patient.
Off-label indications include atrial fibrillation and supraventricular tachycardia.
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| DrugBank Pharmacology: |
After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias. When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival.
Amiodarone prolongs the QRS duration and QT interval. In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited. Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.
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| DrugBank MoA: |
Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.
Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP). In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs. Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.
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| Targets: |
HERG human cardiac K+ channel inhibitor; Beta adrenergic receptor inhibitor&downregulator; Voltage-dependent T-type calcium channel subunit alpha-1I inhibitor; Voltage gated L-type calcium channel inhibitor; Thyroid hormone receptor antagonist&binder; Peroxisome proliferator-activated receptor gamma agonist; Peroxisome proliferator-activated receptor alpha agonist; Peroxisome proliferator-activated receptor gamma coactivator 1-beta agonist
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| Inclusion Criteria: |
Target associated
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