Investigational Drug Details
| Drug ID: | D107 |
| Drug Name: | Digoxin |
| Synonyms: | |
| Type: | small molecule |
| DrugBank ID: | DB00390 |
| DrugBank Description: | Digoxin is one of the oldest cardiovascular medications used today.[A178225] It is a common agent used to manage atrial fibrillation and the symptoms of heart failure.[A178234] Digoxin is classified as a cardiac glycoside and was initially approved by the FDA in 1954.[L6775] This drug originates from the foxglove plant, also known as the _Digitalis_ plant[T610], studied by William Withering, an English physician and botanist in the 1780s.[A178237,A178240] Prior to this, a Welsh family, historically referred to as the _Physicians of Myddvai_, formulated drugs from this plant. They were one of the first to prescribe cardiac glycosides, according to ancient literature dating as early as the 1250s.[A178240] |
| PubChem ID: | 2724385 |
| CasNo: | 20830-75-5 |
| Repositioning for NAFLD: | Yes |
| SMILES: | [H][C@]12CC[C@]3([H])[C@]([H])(C[C@@H](O)[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1 |
| Structure: |
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| InChiKey: | LTMHDMANZUZIPE-PUGKRICDSA-N |
| Molecular Weight: | 780.9385 |
| DrugBank Targets: | Sodium/potassium-transporting ATPase subunit alpha-1 |
| DrugBank MoA: | Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system.[A178234] It reversibly inhibits the Na-K ATPase enzyme, leading to various beneficial effects. The Na-K ATPase enzyme functions to maintain the intracellular environment by regulating the entry and exit of sodium, potassium, and calcium (indirectly). Na-K ATPase is also known as the _sodium pump_[L6775]. The inhibition of the sodium pump by digoxin increases intracellular sodium and increases the calcium level in the myocardial cells, causing an increased contractile force of the heart.[L6775, A178264] This improves the left ventricular ejection fraction (EF), an important measure of cardiac function.[A178234,T613] Digoxin also stimulates the parasympathetic nervous system via the vagus nerve[T607] leading to sinoatrial (SA) and atrioventricular (AV) node effects, decreasing the heart rate.[L6775,A178234] Part of the pathophysiology of heart failure includes neurohormonal activation, leading to an increase in norepinephrine. Digoxin helps to decrease norepinephrine levels through activation of the parasympathetic nervous system.[A178234] |
| DrugBank Pharmacology: | Digoxin is a positive inotropic and negative chronotropic drug[A178234], meaning that it increases the force of the heartbeat and decreases the heart rate.[L6253] The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat.[A178282] The relief of heart failure symptoms during digoxin therapy has been demonstrated in clinical studies by increased exercise capacity and reduced hospitalization due to heart failure and reduced heart failure-related emergency medical visits.[L6775] Digoxin has a narrow therapeutic window.[L6775] **A note on cardiovascular risk** Digoxin poses a risk of rapid ventricular response that can cause ventricular fibrillation in patients with an accessory atrioventricular (AV) pathway. Cardiac arrest as a result of ventricular fibrillation is fatal.[L6775] An increased risk of fatal severe or complete heart block is present in individuals with pre-existing sinus node disease and AV block who take digoxin.[L6775] |
| DrugBank Indication: | Digoxin is indicated in the following conditions: 1) For the treatment of mild to moderate heart failure in adult patients.[L6775] 2) To increase myocardial contraction in children diagnosed with heart failure.[L6775] 3) To maintain control ventricular rate in adult patients diagnosed with chronic atrial fibrillation.[L6775] In adults with heart failure, when it is clinically possible, digoxin should be administered in conjunction with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor for optimum effects.[L6775] |
| Targets: | |
| Therapeutic Category: | |
| Clinical Trial Progress: | |
| Latest Progress: |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L3953 | NCT02315495 | PHASE3 | COMPLETED | NO | 2015-04-03 | 2018-07-06 | Details |
| L5048 | NCT00801164 | PHASE1 | COMPLETED | NO | 2008-12 | 2012-02-02 | Details |
| L5899 | NCT06445946 | PHASE4 | RECRUITING | NO | 2024-08-01 | 2025-02-04 | Details |
| L5966 | NCT00655863 | PHASE3 | COMPLETED | YES | 2007-07 | 2013-05-27 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T06 | Sulfonylurea receptor 1 | ABCC8 | Target is a single protein chain | Q09428 | ABCC8_HUMAN | Details | |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Article ID | PMID | Source | Title |
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