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

Details

Stereochemistry ABSOLUTE
Molecular Formula C43H66O14
Molecular Weight 806.9757
Optical Activity UNSPECIFIED
Defined Stereocenters 20 / 20
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ACETYLDIGITOXIN

SMILES

[H][C@@]1(C[C@H](O)[C@H](O[C@@]2([H])C[C@H](O)[C@H](O[C@@]3([H])C[C@H](OC(C)=O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1)O[C@H]4CC[C@@]5(C)[C@]([H])(CC[C@]6([H])[C@]5([H])CC[C@]7(C)[C@H](CC[C@]67O)C8=CC(=O)OC8)C4

InChI

InChIKey=HPMZBILYSWLILX-UMDUKNJSSA-N
InChI=1S/C43H66O14/c1-21-38(48)33(54-24(4)44)19-37(51-21)57-40-23(3)53-36(18-32(40)46)56-39-22(2)52-35(17-31(39)45)55-27-9-12-41(5)26(16-27)7-8-30-29(41)10-13-42(6)28(11-14-43(30,42)49)25-15-34(47)50-20-25/h15,21-23,26-33,35-40,45-46,48-49H,7-14,16-20H2,1-6H3/t21-,22-,23-,26-,27+,28-,29+,30-,31+,32+,33+,35+,36+,37+,38-,39-,40-,41+,42-,43+/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
n = 10
Health Status: healthy
Age Group: 23 to 29 years
Sex: M
Population Size: 10
Sources:
Other AEs: Color blindness acquired...
Other AEs:
Color blindness acquired
Sources:
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
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
n = 10
Health Status: healthy
Age Group: 23 to 29 years
Sex: M
Population Size: 10
Sources:
Vomiting 22.3%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Diarrhoea 22.9%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Headache 25.1%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Bad dreams 30.2%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Dizziness 33%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Abdominal pain 36.3%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Psychic disorder NOS 36.3%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Anorexia 44.7%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Nausea 45.2%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Muscular weakness 45.8%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Pain retrosternal 5%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Fatigue 53.1%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Visual disorders NEC 53.1%
0.2 mg 2 times / day multiple, oral (mean)
Studied dose
Dose: 0.2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 0.2 mg, 2 times / day
Co-administed with::
digoxin(0.05 mg; 2 tablets per day)
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Sex: M+F
Population Size: 179
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
[Cardiac arrhythmia in old age caused by digitalis intoxication].
1967 Apr 27
Influence of drugs, implanted into the hypothalamus, on the water consumption of rats.
1968 Jan
Atrial dissociation due to digitalis toxicity.
1968 Jun
[On the treatment of the digitalis-induced atrial tachycardia with AV conduction disorder. Experiences with sodium-magnesium aspartate].
1968 Mar 29
Digitoxin induced cardiac necrosis and its inhibition.
1969
[Acute digitalic poisoning].
1970 Feb
[Spironolactone protection against experimental cardiopathy due to digitoxin, disodium phosphate and oil].
1970 Feb
Possible mechanism of the prevention of digitoxin toxicity by spironolactone in the mouse.
1971 Jan
The clinical value of serum digitalis glycoside concentrations in the evaluation of drug toxicity.
1971 Jul 6
Protection by spironolactone and oxandrolone against chronic digitoxin or indomethacin intoxication.
1971 Mar
His bundle electrocardiography during bidirectional tachycardia.
1973 Jul
Effect of microsomal enzyme inducers on the biliary excretion of cardiac glycosides.
1974 Nov
Transient global amnesia associated with cardiac arrhythmia and digitalis intoxication.
1975 Sep-Oct
Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana.
1976
Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments.
1977 Dec
Digitalis delirium: a reminder.
1980 Mar
Effects of atropine on the cardiac arrest induced by propranolol and digitoxin in dogs.
1982
[Digitoxin poisoning: reversing ventricular fibrillation with Fab fragments of anti-digoxin antibody].
1982 Dec 25
Reversal of digitalis-induced mesenteric vasospasm by sodium nitroprusside.
1982 Feb
Effect of age, clonidine or propranolol on behavioral toxicity induced with digitoxin in mice.
1982 Sep
Study of the factors influencing cardiac growth. II. Digitoxin treatment and isoproterenol-induced cardiac hypertrophy in the rat.
1985
Effect of long-term administration of digoxin on exercise performance in chronic airflow obstruction.
1985 Apr
Effect of digitoxin on cardiac arrhythmias in hemodialysis patients.
1987 Nov 16
Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies.
1992
[Digitoxin-induced thrombocytopenia].
1993
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 Jan 8
Hepatorenal syndrome in cirrhotic patients: terlipressine is a safe and efficient treatment; propranolol and digitalic treatments: precipitating and preventing factors?
2000 Oct
Chronic hypertension induced by ouabain but not digoxin in the rat: antihypertensive effect of digoxin and digitoxin.
2000 Sep
Digitoxin medication and cancer; case control and internal dose-response studies.
2001
Treatment of congestive heart failure--current status of use of digitoxin.
2001
Adverse drug reaction monitoring--digitoxin overdosage in the elderly.
2001 Aug
Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells.
2001 Jun
Bidirectional tachycardia: two cases and a review.
2002 Aug
Posterior encephalopathy with vasospasm: MRI and angiography.
2003 Dec
Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells.
2004 May 18
Bidirectional ventricular tachycardia due to digitalis intoxication.
2005 Feb
Iatrogenic sick sinus syndrome.
2007 May
Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels.
2008 Feb 19
Digitoxin elicits anti-inflammatory and vasoprotective properties in endothelial cells: Therapeutic implications for the treatment of atherosclerosis?
2009 Oct
Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata.
2011 Oct
Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells.
2012 Jan 1
Ouabain, a cardiac glycoside, inhibits the Fanconi anemia/BRCA pathway activated by DNA interstrand cross-linking agents.
2013
Interaction of digitalis-like compounds with p-glycoprotein.
2013 Feb
A novel cell-based high-throughput screen for inhibitors of HIV-1 gene expression and budding identifies the cardiac glycosides.
2014 Apr
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 Jun
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
ACETYLDIGITOXIN
INN   MART.   ORANGE BOOK   WHO-DD  
INN  
Official Name English
ACETYLDIGITOXIN [MART.]
Common Name English
(3.BETA.,5.BETA.)-3-((O-3-O-ACETYL-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
Acetyldigitoxin [WHO-DD]
Common Name English
ACETYLDIGITOXINS .ALPHA.-FORM
MI  
Common Name English
ACETYLDIGITOXINS .ALPHA.-FORM [MI]
Common Name English
acetyldigitoxin [INN]
Common Name English
ACYLANID
Brand Name English
ACETYLDIGITOXIN [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-VATC QC01AA01
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
WHO-ATC C01AA01
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
NCI_THESAURUS C66894
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
Code System Code Type Description
FDA UNII
0ZV4Q4L2FU
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
WIKIPEDIA
ACETYLDIGITOXIN
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
ChEMBL
CHEMBL3545057
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
CHEBI
53773
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
DAILYMED
0ZV4Q4L2FU
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
EVMPD
SUB05230MIG
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
DRUG CENTRAL
67
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
DRUG BANK
DB00511
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
MERCK INDEX
m1354
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY Merck Index
CAS
1111-39-3
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
EPA CompTox
DTXSID6022551
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
ECHA (EC/EINECS)
214-178-4
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
IUPHAR
6794
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
SMS_ID
100000084600
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
PUBCHEM
5284512
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
INN
792
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
NCI_THESAURUS
C65212
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY
RXCUI
132871
Created by admin on Fri Dec 15 15:39:34 UTC 2023 , Edited by admin on Fri Dec 15 15:39:34 UTC 2023
PRIMARY RxNorm