Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C41H64O13 |
| Molecular Weight | 764.9391 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 20 / 20 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H]1O[C@H](C[C@H](O)[C@@H]1O)O[C@H]2[C@@H](O)C[C@H](O[C@H]3[C@@H](O)C[C@H](O[C@H]4CC[C@@]5(C)[C@H](CC[C@@H]6[C@@H]5CC[C@]7(C)[C@H](CC[C@]67O)C8=CC(=O)OC8)C4)O[C@@H]3C)O[C@@H]2C
InChI
InChIKey=WDJUZGPOPHTGOT-XUDUSOBPSA-N
InChI=1S/C41H64O13/c1-20-36(46)29(42)16-34(49-20)53-38-22(3)51-35(18-31(38)44)54-37-21(2)50-33(17-30(37)43)52-25-8-11-39(4)24(15-25)6-7-28-27(39)9-12-40(5)26(10-13-41(28,40)47)23-14-32(45)48-19-23/h14,20-22,24-31,33-38,42-44,46-47H,6-13,15-19H2,1-5H3/t20-,21-,22-,24-,25+,26-,27+,28-,29+,30+,31+,33+,34+,35+,36-,37-,38-,39+,40-,41+/m1/s1
| Molecular Formula | C41H64O13 |
| Molecular Weight | 764.9391 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 20 / 20 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.medscape.com/viewarticle/842364
Curator's Comment: description was created based on several sources, including
http://www.medscape.com/viewarticle/842364
Digoxin is a cardiac glycoside derived from the purple foxglove flower. In 1785, the English chemist, botanist, and physician Sir William Withering published his findings that Digitalis purpurea could be used to treat cardiac dropsy (congestive heart failure; CHF). Digoxin has been in use for many years, but was not approved by the FDA for treatment of heart failure (HF) until the late 1990s. Another FDA indication for digoxin is atrial fibrillation (AF). Digoxin also has numerous off-label uses, such as in fetal tachycardia, supra-ventricular tachycardia, cor pulmonale, and pulmonary hypertension. Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digoxin also has Para sympathomimetic properties. By increasing vagal tone in the sinoatrial and atrioventricular (AV) nodes, it slows the heart rate and AV nodal conduction.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2095186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19751721 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CRYSTODIGIN Approved UseIn adults, digoxin is indicated for the treatment of mild to moderate heart failure and for the control of resting ventricular rate in patients with chronic atrial fibrillation. (1). In pediatric patients with heart failure, digoxin increases myocardial contractility |
|||
| Diagnostic | CRYSTODIGIN Approved UseIn adults, digoxin is indicated for the treatment of mild to moderate heart failure and for the control of resting ventricular rate in patients with chronic atrial fibrillation. (1). In pediatric patients with heart failure, digoxin increases myocardial contractility |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.76 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18823299/ |
0.25 mg 1 times / day steady-state, oral dose: 0.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ETORICOXIB |
DIGITOXIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1.32 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18823299/ |
0.25 mg 1 times / day steady-state, oral dose: 0.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
DIGITOXIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
13.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18823299/ |
0.25 mg 1 times / day steady-state, oral dose: 0.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ETORICOXIB |
DIGITOXIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
12.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18823299/ |
0.25 mg 1 times / day steady-state, oral dose: 0.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
DIGITOXIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
9.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/914188/ |
0.5 mg single, intravenous dose: 0.5 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
DIGITOXIN unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7.4 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/914188/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIGITOXIN unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
9.7 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/914188/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
DIGITOXIN unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
0.1 mg 1 times / day multiple, oral Studied dose Dose: 0.1 mg, 1 times / day Route: oral Route: multiple Dose: 0.1 mg, 1 times / day Sources: |
healthy, 23 to 29 years Health Status: healthy Age Group: 23 to 29 years Sex: M Sources: |
Other AEs: Color blindness acquired... |
0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
Other AEs: Fatigue, Visual disorders NEC... Other AEs: Fatigue (53.1%) Sources: Visual disorders NEC (53.1%) Muscular weakness (45.8%) Nausea (45.2%) Anorexia (44.7%) Psychic disorder NOS (36.3%) Abdominal pain (36.3%) Dizziness (33%) Bad dreams (30.2%) Headache (25.1%) Diarrhoea (22.9%) Vomiting (22.3%) Pain retrosternal (5%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Color blindness acquired | 0.1 mg 1 times / day multiple, oral Studied dose Dose: 0.1 mg, 1 times / day Route: oral Route: multiple Dose: 0.1 mg, 1 times / day Sources: |
healthy, 23 to 29 years Health Status: healthy Age Group: 23 to 29 years Sex: M Sources: |
|
| Vomiting | 22.3% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Diarrhoea | 22.9% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Headache | 25.1% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Bad dreams | 30.2% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Dizziness | 33% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Abdominal pain | 36.3% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Psychic disorder NOS | 36.3% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Anorexia | 44.7% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Nausea | 45.2% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Muscular weakness | 45.8% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Pain retrosternal | 5% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Fatigue | 53.1% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
| Visual disorders NEC | 53.1% | 0.2 mg 2 times / day multiple, oral Studied dose Dose: 0.2 mg, 2 times / day Route: oral Route: multiple Dose: 0.2 mg, 2 times / day Sources: |
unhealthy, adult |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes [IC50 14.2 uM] | ||||
| yes [IC50 36 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015-06 |
|
| A novel cell-based high-throughput screen for inhibitors of HIV-1 gene expression and budding identifies the cardiac glycosides. | 2014-04 |
|
| Interaction of digitalis-like compounds with p-glycoprotein. | 2013-02 |
|
| Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents. | 2013 |
|
| Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells. | 2012-01-01 |
|
| Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata. | 2011-10 |
|
| Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: Therapeutic implications for the treatment of atherosclerosis? | 2009-10 |
|
| Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels. | 2008-02-19 |
|
| Iatrogenic sick sinus syndrome. | 2007-05 |
|
| Bidirectional ventricular tachycardia due to digitalis intoxication. | 2005-02 |
|
| Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. | 2004-05-18 |
|
| Posterior encephalopathy with vasospasm: MRI and angiography. | 2003-12 |
|
| Bidirectional tachycardia: two cases and a review. | 2002-08 |
|
| Adverse drug reaction monitoring--digitoxin overdosage in the elderly. | 2001-08 |
|
| Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. | 2001-06 |
|
| Digitoxin medication and cancer; case control and internal dose-response studies. | 2001 |
|
| Treatment of congestive heart failure--current status of use of digitoxin. | 2001 |
|
| Hepatorenal syndrome in cirrhotic patients: terlipressine is a safe and efficient treatment; propranolol and digitalic treatments: precipitating and preventing factors? | 2000-10 |
|
| Chronic hypertension induced by ouabain but not digoxin in the rat: antihypertensive effect of digoxin and digitoxin. | 2000-09 |
|
| Synthesis of 20-hydroxy-, 20-amino-, and 20-nitro-14-hydroxy-21-nor-5 beta,14 beta-pregnane C-3 glycosides and related derivatives: structure-activity relationships of pregnanes that bind to the digitalis receptor. | 1993-01-08 |
|
| [Digitoxin-induced thrombocytopenia]. | 1993 |
|
| Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies. | 1992 |
|
| Effect of digitoxin on cardiac arrhythmias in hemodialysis patients. | 1987-11-16 |
|
| Effect of long-term administration of digoxin on exercise performance in chronic airflow obstruction. | 1985-04 |
|
| Study of the factors influencing cardiac growth. II. Digitoxin treatment and isoproterenol-induced cardiac hypertrophy in the rat. | 1985 |
|
| [Digitoxin poisoning: reversing ventricular fibrillation with Fab fragments of anti-digoxin antibody]. | 1982-12-25 |
|
| Effect of age, clonidine or propranolol on behavioral toxicity induced with digitoxin in mice. | 1982-09 |
|
| Reversal of digitalis-induced mesenteric vasospasm by sodium nitroprusside. | 1982-02 |
|
| Effects of atropine on the cardiac arrest induced by propranolol and digitoxin in dogs. | 1982 |
|
| Digitalis delirium: a reminder. | 1980-03 |
|
| Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. | 1977-12 |
|
| Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana. | 1976 |
|
| Transient global amnesia associated with cardiac arrhythmia and digitalis intoxication. | 1975-09-01 |
|
| Effect of microsomal enzyme inducers on the biliary excretion of cardiac glycosides. | 1974-11 |
|
| His bundle electrocardiography during bidirectional tachycardia. | 1973-07 |
|
| The clinical value of serum digitalis glycoside concentrations in the evaluation of drug toxicity. | 1971-07-06 |
|
| Protection by spironolactone and oxandrolone against chronic digitoxin or indomethacin intoxication. | 1971-03 |
|
| Possible mechanism of the prevention of digitoxin toxicity by spironolactone in the mouse. | 1971-01 |
|
| [Acute digitalic poisoning]. | 1970-02 |
|
| [Spironolactone protection against experimental cardiopathy due to digitoxin, disodium phosphate and oil]. | 1970-02 |
|
| Digitoxin induced cardiac necrosis and its inhibition. | 1969 |
|
| Atrial dissociation due to digitalis toxicity. | 1968-06 |
|
| [On the treatment of the digitalis-induced atrial tachycardia with AV conduction disorder. Experiences with sodium-magnesium aspartate]. | 1968-03-29 |
|
| Influence of drugs, implanted into the hypothalamus, on the water consumption of rats. | 1968-01 |
|
| [Cardiac arrhythmia in old age caused by digitalis intoxication]. | 1967-04-27 |
Patents
Sample Use Guides
Age Oral Loading Dose, mcg/kg
Premature: 20 - 30; Full-Term 25 - 35; 1 to 24 months 35 - 60; 2 to 5 years 30 - 45; 5 to 10 years 20 - 35; Over 10 years 10 - 15
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23858296
Curator's Comment: digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter
Unknown
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:33:52 GMT 2025
by
admin
on
Mon Mar 31 18:33:52 GMT 2025
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| Record UNII |
E90NZP2L9U
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| Record Status |
Validated (UNII)
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| Classification Tree | Code System | Code | ||
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CFR |
21 CFR 862.3300
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WHO-VATC |
QC01AA04
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FDA ORPHAN DRUG |
205005
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FDA ORPHAN DRUG |
149601
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NCI_THESAURUS |
C471
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NCI_THESAURUS |
C78322
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WHO-ATC |
C01AA04
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LIVERTOX |
306
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FDA ORPHAN DRUG |
149701
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215
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3403
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m4452
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145796
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881
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1547
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DB01396
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DTXSID0022933
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DIGITOXIN
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PRIMARY | Description: A white or almost white, microcrystalline powder; odourless.Solubility: Practically insoluble in water; slightly soluble in ethanol (~750 g/l) TS.Category: Cardiotonic.Storage: Digitoxin should be kept in a well-closed container, protected from light.Additional information: CAUTION: Digitoxin is extremely poisonous and should be handled with care.Requirements: Definition. Digitoxin contains not less than 95.0% and not more than 105.0% of C41H64O13, calculated with reference to the dried substance. | ||
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CHEMBL254219
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441207
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100000092778
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E90NZP2L9U
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28544
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C2634
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D004074
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200-760-5
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7529
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DIGITOXIN
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6782
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1199002
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SUB07133MIG
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METABOLIC ENZYME -> SUBSTRATE | |||
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PARENT -> IMPURITY |
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ACTIVE MOIETY |