ContaminantDB: Digoxin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (23)XML

Record Information

Version

1.0

Creation Date

2009-07-15 20:45:04 UTC

Update Date

2026-05-14 16:37:20 UTC

Accession Number

CHEM002115

Identification

Common Name

Digoxin

Class

Small Molecule

Description

Digoxin is a cardiac glycoside extracted from the foxglove plant, digitalis. It is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and congestive heart failure that cannot be controlled by other medication. Digoxin preparations are commonly marketed under the trade name Lanoxin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) Digoxin is a cardiotonic glycoside obtained mainly from Digitalis lanata; It consists of three sugars and the aglycone digoxigenin. Digoxin binds to a site on the extracellular aspect of the of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This is a different mechanism from that of catecholamines. Owing to its narrow therapeutic index (the margin between effectiveness and toxicity), side effects of digoxin are inevitable. Nausea, vomiting and GIT upset are common, especially in higher doses. Decreased conduction in the AV node can lead to AV blocks, increased intracellular Ca2+ causes a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation. An often described but rarely seen side effect of digoxin is a disturbance of color vision (mostly yellow and green color) called xanthopsia.

Contaminant Sources

Clean Air Act Chemicals
FooDB Chemicals
HMDB Contaminants - Urine
IARC Carcinogens Group 2B
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Anti-Arrhythmia Agent
Cardiotonic Agent
Drug
Enzyme Inhibitor
Ester
Food Toxin
Human Neurotoxin
Metabolite
Natural Compound
Organic Compound
PFAS
Phytotoxin
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
12beta-Hydroxydigitoxin	ChEBI
Lanoxicaps	Kegg
Lanoxin	Kegg
12b-Hydroxydigitoxin	Generator
12Β-hydroxydigitoxin	Generator
Cardoxin	HMDB
Cogoxin	HMDB
Davoxin	HMDB
Digacin	HMDB
Digitalis glycoside	HMDB
Digoxin pediatric	HMDB
Dilanacin	HMDB
Dynamos	HMDB
Eudigox	HMDB
Homolle'S digitalin	HMDB
Lanacrist	HMDB
Lanicor	HMDB
Neo-lanicor	HMDB
Rougoxin	HMDB
SK-Digoxin	HMDB
Vanoxin	HMDB
AWD.pharma brand OF digoxin	HMDB
Boehringer, digoxina	HMDB
Hemigoxine nativelle	HMDB
Nativelle, hemigoxine	HMDB
Novartis brand OF digoxin	HMDB
Roche brand OF digoxin	HMDB
Teofarma brand OF digoxin	HMDB
Lanoxin PG	HMDB
Lanoxin-PG	HMDB
R.A.N. brand OF digoxin	HMDB
Digoregen	HMDB
Digoxina boehringer	HMDB
Kern brand OF digoxin	HMDB
Lanacordin	HMDB
Lilly brand OF digoxin	HMDB
Mapluxin	HMDB
Proctor and gamble brand OF digoxin	HMDB
UDL brand OF digoxin	HMDB
Virco brand OF digoxin	HMDB
Bertek brand OF digoxin	HMDB
Digitek	HMDB
Digoxine nativelle	HMDB
Glaxo wellcome brand OF digoxin	HMDB
GlaxoSmithKline brand 1 OF digoxin	HMDB
GlaxoSmithKline brand 2 OF digoxin	HMDB
Lenoxin	HMDB
Nativelle, digoxine	HMDB

Chemical Formula

C₄₁H₆₄O₁₄

Average Molecular Mass

780.939 g/mol

Monoisotopic Mass

780.430 g/mol

CAS Registry Number

20830-75-5

IUPAC Name

4-[(1R,3aS,3bR,5aR,7S,9aS,9bS,11R,11aS)-7-{[(2R,4S,5S,6R)-5-{[(2S,4S,5S,6R)-5-{[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-4-hydroxy-6-methyloxan-2-yl]oxy}-4-hydroxy-6-methyloxan-2-yl]oxy}-3a,11-dihydroxy-9a,11a-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]-2,5-dihydrofuran-2-one

Traditional Name

digoxin

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

InChI Identifier

InChI=1S/C41H64O14/c1-19-36(47)28(42)15-34(50-19)54-38-21(3)52-35(17-30(38)44)55-37-20(2)51-33(16-29(37)43)53-24-8-10-39(4)23(13-24)6-7-26-27(39)14-31(45)40(5)25(9-11-41(26,40)48)22-12-32(46)49-18-22/h12,19-21,23-31,33-38,42-45,47-48H,6-11,13-18H2,1-5H3/t19-,20-,21-,23-,24+,25-,26-,27+,28+,29+,30+,31-,33+,34+,35+,36-,37-,38-,39+,40+,41+/m1/s1

InChI Key

LTMHDMANZUZIPE-PUGKRICDSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as cardenolide glycosides and derivatives. Cardenolide glycosides and derivatives are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Steroids and steroid derivatives

Sub Class

Steroid lactones

Direct Parent

Cardenolide glycosides and derivatives

Alternative Parents

Substituents

Cardanolide-glycoside
Steroidal glycoside
Oligosaccharide
12-hydroxysteroid
14-hydroxysteroid
Hydroxysteroid
Glycosyl compound
O-glycosyl compound
2-furanone
Oxane
Cyclic alcohol
Dihydrofuran
Alpha,beta-unsaturated carboxylic ester
Enoate ester
Tertiary alcohol
Lactone
Carboxylic acid ester
Secondary alcohol
Organoheterocyclic compound
Oxacycle
Acetal
Carboxylic acid derivative
Monocarboxylic acid or derivatives
Hydrocarbon derivative
Alcohol
Organic oxide
Organic oxygen compound
Carbonyl group
Organooxygen compound
Aliphatic heteropolycyclic compound

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

steroid saponin (CHEBI:4551 )
cardenolide glycoside (CHEBI:4551 )
cardanolide (C06956 )
Cardanolides and derivatives (C06956 )
Cardanolide and derivatives (C06956 )
Cardiac glycosides (C06956 )
Terpenoids (C06956 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Hypothalamus
Kidney
Liver
Platelet
Small Intestine

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor

Physical Properties

State

Solid

Appearance

Colorless to white crystals; or white crystalline powder (1).

Experimental Properties

Property	Value
Melting Point	217-221°C
Boiling Point	Not Available
Solubility	64.8 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.13 g/L	ALOGPS
logP	1.04	ALOGPS
logP	2.37	ChemAxon
logS	-3.8	ALOGPS
pKa (Strongest Acidic)	7.15	ChemAxon
pKa (Strongest Basic)	-3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	13	ChemAxon
Hydrogen Donor Count	6	ChemAxon
Polar Surface Area	203.06 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	193.23 m³·mol⁻¹	ChemAxon
Polarizability	84.8 Å³	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_4) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_5) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_6) - 70eV, Positive	Not Available	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0h9s-0004022900-fb7295b1343cfcb0f262	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00ec-0209043100-9967a858c77340d2fab3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-007o-1419132100-e5de5e30c4299c931671	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01tj-0114011900-e0edd63658065bb869f3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01bj-2519564400-bd5189ac4cf921dbac79	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014i-6105930000-b03a6876fb182cec49e1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-01q9-0113000900-5c07bff161d1ddd9c50e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01q9-2911000400-fe987c159da70447f56d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-005a-6942010000-377898578023a42020d5	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00os-0501095500-c884ce473f948cad43ce	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-4900011400-932fc5fee2cbc1e58a5a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004l-5900001400-b3251bf0b534b08a8db8	Spectrum

Toxicity Profile

Route of Exposure

Injestion or dermal contact. (26) Absorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets).

Mechanism of Toxicity

Digoxin binds to a site on the extracellular aspect of the alpha-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes) and decreases its function. This causes an increase in the level of sodium ions in the myocytes. This effect causes an increase in the length the cardiac action potential, which when combined with the effects of digoxin on the parasympathetic nervous system, lead to a decrease in heart rate. Increased amounts of calcium are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This leads to increased contractility of the heart. Digoxin also increases vagal activity via its action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. (24)

Metabolism

Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. Route of Elimination: Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Half Life: 3.5 to 5 days

Toxicity Values

LD₅₀ = 7.8 mg/kg (orally in mice).

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2B, possibly carcinogenic to humans. (23)

Uses/Sources

For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure. Digoxin is a plant toxin found in the foxglove plant (Digitalis lanata). It is used as a drug to treat various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure. (24)

Minimum Risk Level

Not Available

Health Effects

Digoxin mainly affects the heart. (24)

Symptoms

Adverse affects of digoxin include loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities. (24)

Treatment

Treatment of dioxin overdose includes supportive measure and administration of the antidote, antidigoxin (DIGIBIND). Toxicity can also be treated with higher than normal doses of potassium. (24)

Concentrations

Not Available

External Links

DrugBank ID

DB00390

HMDB ID

HMDB0001917

FooDB ID

FDB022736

Phenol Explorer ID

Not Available

KNApSAcK ID

C00003618

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

2047

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Wolfgang Voigtlander, Fritz Kaiser, Wolfgang Schaumann, Kurt Stach, “Preparation of C22-alkyl derivative of digoxin.” U.S. Patent US3981862, issued October, 1972.

MSDS

Link

General References

1. https://www.ncbi.nlm.nih.gov/pubmed/?term=10438974

2. https://www.ncbi.nlm.nih.gov/pubmed/?term=16970134

3. https://www.ncbi.nlm.nih.gov/pubmed/?term=7739045

4. https://www.ncbi.nlm.nih.gov/pubmed/?term=8234291

5. Kurup RK, Kurup PA: Hypothalamic digoxin and isoprenoid pathway dysfunction relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration--relation to hemispheric chemical dominance. Int J Neurosci. 2003 Apr;113(4):547-63.

6. Weber P, Lettieri JT, Kaiser L, Mazzu AL: Lack of mutual pharmacokinetic interaction between cerivastatin, a new HMG-CoA reductase inhibitor, and digoxin in healthy normocholesterolemic volunteers. Clin Ther. 1999 Sep;21(9):1563-75.

7. Pahkla R, Irs A, Oselin K, Rootslane L: Digoxin: use pattern in Estonia and bioavailability of the local market leader. J Clin Pharm Ther. 1999 Oct;24(5):375-80.

8. Jablecka A, Chmara E, Korzeniowska K: The level of plasma neuroendocrine activity and the concentration of digoxin in the serum of patients with mild chronic heart failure. Int J Clin Pharmacol Res. 1998;18(4):171-8.

9. Bachmakov I, Rekersbrink S, Hofmann U, Eichelbaum M, Fromm MF: Characterisation of (R/S)-propafenone and its metabolites as substrates and inhibitors of P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2005 Mar;371(3):195-201. Epub 2005 Apr 15.