Investigational Drug Details
| Drug ID: | D112 |
| Drug Name: | Digoxin |
| Synonyms: | 12β-hydroxydigitoxin; Digoxin |
| Type: | Chemical drug |
| DrugBank ID: | DB00390 |
| DrugBank Description: | Digoxin is one of the oldest cardiovascular medications used today. It is a common agent used to manage atrial fibrillation and the symptoms of heart failure. Digoxin is classified as a cardiac glycoside and was initially approved by the FDA in 1954. This drug originates from the foxglove plant, also known as the _Digitalis_ plant, studied by William Withering, an English physician and botanist in the 1780s. 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. |
| PubChem ID: | 2724385 |
| CasNo: | 20830-75-5 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O[C@]12[C@@](C)([C@H](CC2)C2=CC(=O)OC2)[C@H](O)C[C@H]2[C@H]1CC[C@H]1[C@]2(C)CC[C@@H](C1)O[C@H]1C[C@H](O)[C@@H]([C@H](O1)C)O[C@H]1C[C@H](O)[C@@H]([C@H](O1)C)O[C@H]1C[C@H](O)[C@@H]([C@H](O1)C)O |
| Structure: |
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| InChiKey: | LTMHDMANZUZIPE-PUGKRICDSA-N |
| Molecular Weight: | 780.949 |
| DrugBank Targets: | Sodium/potassium-transporting ATPase subunit alpha-1 inhibitor |
| DrugBank MoA: | Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system. 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_. 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. This improves the left ventricular ejection fraction (EF), an important measure of cardiac function. Digoxin also stimulates the parasympathetic nervous system via the vagus nerve leading to sinoatrial (SA) and atrioventricular (AV) node effects, decreasing the heart rate. 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. |
| DrugBank Pharmacology: | Digoxin is a positive inotropic and negative chronotropic drug, meaning that it increases the force of the heartbeat and decreases the heart rate. The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat. 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. Digoxin has a narrow therapeutic window. **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. 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. |
| DrugBank Indication: | Digoxin is indicated in the following conditions: 1) For the treatment of mild to moderate heart failure in adult patients. 2) To increase myocardial contraction in children diagnosed with heart failure. 3) To maintain control ventricular rate in adult patients diagnosed with chronic atrial fibrillation. 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. |
| Targets: | ATP1A1 inhibitor; ATP1A2 inhibitor; ATP1A3 inhibitor; ATP1A4 inhibitor |
| Therapeutic Category: | Antiarrhythmic |
| Clinical Trial Progress: | Phase 2 on-going (NCT04216693: These data identify PKM2 as a mediator and therapeutic target for regulating liver sterile inflammation, and demonstrate a novel role for digoxin that can effectively protect the liver from ASH and NASH.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0296 | NCT04972396 | Phase 1 | Recruiting | No Results Available | October 5, 2021 | November 16, 2021 | Details |
| L0444 | NCT04216693 | Phase 2 | Not recruiting | No Results Available | 31/12/2019 | 12 December 2020 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01791 | 34616724 | Front Cell Dev Biol | Comprehensive Analysis of NAFLD and the Therapeutic Target Identified. | Details |
| A03666 | 33914974 | Fundam Clin Pharmacol | Changes in digoxin pharmacokinetics associated with hepatic P-glycoprotein upregulation in rats with non-alcoholic fatty liver disease. | Details |
| A10250 | 31411894 | Am J Physiol Gastrointest Liver Physiol | Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. | Details |
| A14410 | 29420067 | Am J Physiol Gastrointest Liver Physiol | Organic solute transporter OSTα/β is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. | Details |
| A14421 | 29414684 | Cell Metab | Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. | Details |
| A40599 | 4078725 | J Pharmacol Exp Ther | Effect of an aminocardenolide and digoxin upon atrioventricular refractory period in the dog. | Details |