U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of Digitoxin

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

HIDE SMILES / InChI

Description
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

Sources: doi/10.1002/clc.4960020211/pdf

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CRYSTODIGIN

Approved Use

In 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 Use

In 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

Cmax

ValueDoseCo-administeredAnalytePopulation
1.76 ng/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
13.3 ng × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
9.5 day
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
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
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

Doses

DosePopulationAdverse 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...
Other AEs:
Color blindness acquired
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Other AEs: Fatigue, Visual disorders NEC...
Other AEs:
Fatigue (53.1%)
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%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
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
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 14.2 uM]
yes [IC50 36 uM]
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Curator's Comment: digitoxin inhibits interaction of NFAT1 with the proximal c-MYC promoter
Unknown
Name Type Language
DIGITOXINUM
HPUS   WHO-IP LATIN  
Preferred Name English
Digitoxin
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN  
Official Name English
TRADIGAL
Common Name English
CRYSTODIGIN
Code English
DIGIMERCK
Common Name English
DIGITOXINUM [HPUS]
Common Name English
UNIDIGIN
Common Name English
CARD-20(22)-ENOLIDE, 3-((O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-14-HYDROXY-, (3.BETA.,5.BETA.)-
Common Name English
(3.BETA.,5.BETA.)-3-((O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-14-HYDROXYCARD-20(22)-ENOLIDE
Common Name English
DIGITALIN, CRYSTALLINE
Common Name English
DIGITOXIN [WHO-IP]
Common Name English
DIGITOXIN [MI]
Common Name English
DIGITOXIN [EP MONOGRAPH]
Common Name English
DIGITOXIN [JAN]
Common Name English
(3.BETA.,5.BETA.)-3-((O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXAPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-14-HYDROXYCARD-20(22)-ENOLIDE
Common Name English
DIGITOXOSIDE
Common Name English
Digitoxin [WHO-DD]
Common Name English
DIGITOXIN [USP IMPURITY]
Common Name English
DIGITOPHYLLIN
Common Name English
GLUCODIGIN
Common Name English
DIGITOXIN [ORANGE BOOK]
Common Name English
DIGITOXIN [USP MONOGRAPH]
Common Name English
DIGITOXIN [HSDB]
Common Name English
DIGITOXIN [USP-RS]
Common Name English
DIGOXIN IMPURITY A [EP IMPURITY]
Common Name English
DIGITOXINUM [WHO-IP LATIN]
Common Name English
DIGITOXIN [VANDF]
Common Name English
digitoxin [INN]
Common Name English
NSC-7529
Code English
PURPURID
Common Name English
3.BETA.-((2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-14-HYDROXY-5.BETA.-CARD-20(22)-ENOLIDE
Systematic Name English
LANATOXIN
Common Name English
CRISTAPURAT
Common Name English
Classification Tree Code System Code
CFR 21 CFR 862.3300
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
WHO-VATC QC01AA04
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
FDA ORPHAN DRUG 205005
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FDA ORPHAN DRUG 149601
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
NCI_THESAURUS C471
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
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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Code System Code Type Description
HSDB
215
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PRIMARY
RXCUI
3403
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PRIMARY RxNorm
MERCK INDEX
m4452
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PRIMARY Merck Index
CHEBI
145796
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PRIMARY
DRUG CENTRAL
881
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PRIMARY
INN
1547
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PRIMARY
DRUG BANK
DB01396
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PRIMARY
EPA CompTox
DTXSID0022933
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PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
DIGITOXIN
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
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.
FDA UNII
E90NZP2L9U
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PRIMARY
CAS
71-63-6
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PRIMARY
ChEMBL
CHEMBL254219
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PRIMARY
PUBCHEM
441207
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PRIMARY
SMS_ID
100000092778
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PRIMARY
DAILYMED
E90NZP2L9U
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PRIMARY
CHEBI
28544
Created by admin on Mon Mar 31 18:33:52 GMT 2025 , Edited by admin on Mon Mar 31 18:33:52 GMT 2025
PRIMARY
NCI_THESAURUS
C2634
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PRIMARY
MESH
D004074
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PRIMARY
ECHA (EC/EINECS)
200-760-5
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PRIMARY
NSC
7529
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PRIMARY
WIKIPEDIA
DIGITOXIN
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PRIMARY
IUPHAR
6782
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PRIMARY
RS_ITEM_NUM
1199002
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PRIMARY
EVMPD
SUB07133MIG
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PRIMARY