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Record Information
Version3.6
Creation Date2006-05-18 08:19:31 UTC
Update Date2016-02-11 01:05:05 UTC
HMDB IDHMDB01917
Secondary Accession Numbers
  • HMDB14534
Metabolite Identification
Common NameDigoxin
DescriptionDigoxin 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) -- Pubchem; 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. -- Wikipedia; 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.
Structure
Thumb
Synonyms
ValueSource
12beta-HydroxydigitoxinChEBI
12b-HydroxydigitoxinGenerator
12β-hydroxydigitoxinGenerator
CardoxinHMDB
CogoxinHMDB
DavoxinHMDB
DigacinHMDB
Digitalis glycosideHMDB
Digoxin pediatricHMDB
DilanacinHMDB
DynamosHMDB
EudigoxHMDB
Homolle'S digitalinHMDB
LanacristHMDB
LanicorHMDB
LanoxicapsHMDB
LanoxinHMDB
neo-LanicorHMDB
RougoxinHMDB
SK-DigoxinHMDB
VanoxinHMDB
Chemical FormulaC41H64O14
Average Molecular Weight780.9385
Monoisotopic Molecular Weight780.429606756
IUPAC Name4-[(1S,2S,5S,7R,10R,11S,14R,15S,16R)-5-{[(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}-11,16-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]-2,5-dihydrofuran-2-one
Traditional Namedigoxin
CAS Registry Number20830-75-5
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 KeyInChIKey=LTMHDMANZUZIPE-PUGKRICDSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cardenolide glycosides and derivatives. These are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassSteroid lactones
Direct ParentCardenolide glycosides and derivatives
Alternative Parents
Substituents
  • Cardanolide-glycoside
  • Steroidal glycoside
  • Oligosaccharide
  • Hydroxysteroid
  • 12-hydroxysteroid
  • Oxane
  • Saccharide
  • 2-furanone
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Tertiary alcohol
  • Dihydrofuran
  • Cyclic alcohol
  • Secondary alcohol
  • Lactone
  • Carboxylic acid ester
  • 1,2-diol
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Plant
Biofunction
  • Anti-Arrhythmia Agents
  • Antiarrhythmic Agents
  • Cardiotonic Agents
  • Cell signalling
  • Enzyme Inhibitors
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
Application
  • Nutrients
  • Pharmaceutical
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point249 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0648 mg/mL at 25 °CNot Available
LogP1.26SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.13 mg/mLALOGPS
logP1.04ALOGPS
logP2.37ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.15ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area203.06 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity193.23 m3·mol-1ChemAxon
Polarizability84.8 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
Tissue Location
  • Hypothalamus
  • Kidney
  • Liver
  • Platelet
  • Small Intestine
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0007 +/- 0.00007 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0014 +/- 0.0001 uMAdult (>18 years old)BothHeart failure details
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease References
Heart failure
  1. Adams KF Jr, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB: Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol. 2002 Mar 20;39(6):946-53. [11897434 ]
Associated OMIM IDsNone
DrugBank IDDB00390
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022736
KNApSAcK IDNot Available
Chemspider ID2006532
KEGG Compound IDC06956
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDigoxin
NuGOwiki LinkHMDB01917
Metagene LinkHMDB01917
METLIN ID2047
PubChem Compound2724385
PDB IDDGX
ChEBI ID4551
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [14993604 ]
  2. 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. [15900513 ]
  3. 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. [12856482 ]
  4. 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. [10509851 ]
  5. 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. [10583701 ]
  6. 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. [10052027 ]
  7. Kurup RK, Kurup PA: Hypothalamic digoxin and hemispheric chemical dominance: relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Int J Neurosci. 2003 Aug;113(8):1105-25. [12888425 ]
  8. Chirinos JA, Castrellon A, Zambrano JP, Jimenez JJ, Jy W, Horstman LL, Willens HJ, Castellanos A, Myerburg RJ, Ahn YS: Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation. Heart Rhythm. 2005 May;2(5):525-9. [15840479 ]
  9. Dasgupta A, Trejo O: Suppression of total digoxin concentrations by digoxin-like immunoreactive substances in the MEIA digoxin assay. Elimination of negative interference by monitoring free digoxin concentrations. Am J Clin Pathol. 1999 Mar;111(3):406-10. [10078117 ]
  10. Ravikumar A, Kurup PA: The isoprenoid pathway in lone atrial fibrillation with embolic stroke. Indian Heart J. 2001 Mar-Apr;53(2):184-8. [11428474 ]
  11. Cuena Boy R, Martin Montero Mdel P: [Digoxin dosing in the aged: new pharmacokinetic system versus Jellife and Koup methods] Invest Clin. 2003 Mar;44(1):31-9. [12703181 ]
  12. Bentur Y, Tsipiniuk A, Taitelman U: Postmortem digoxin-like immunoreactive substances (DLIS) in patients not treated with digoxin. Hum Exp Toxicol. 1999 Feb;18(2):67-70. [10100017 ]
  13. Johnson RD, Dorr MB, Hunt TL, Conway S, Talbot GH: Pharmacokinetic interaction of sparfloxacin and digoxin. Clin Ther. 1999 Feb;21(2):368-79. [10211539 ]
  14. Mrozikiewicz A: Endogenous drug-like factors. Pol J Pharmacol. 1998 Nov-Dec;50(6):393-7. [10385921 ]
  15. Peters J, Welker HA, Bullingham R: Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradil-digoxin therapy at therapeutic doses. Eur J Drug Metab Pharmacokinet. 1999 Apr-Jun;24(2):133-40. [10510740 ]
  16. Cuena Boy R, Ortiz de Apodaca Ruiz MA, Macia Martinez MA: [Best result of digoxin dosing in the aged by taking into account that both the elimination as well as the volume of distribution of the drug decrease when the kidney function deteriorates] An Med Interna. 2002 Jul;19(7):331-5. [12224140 ]
  17. Kurup RK, Kurup PA: Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease. Int J Neurosci. 2003 Sep;113(9):1221-40. [12959741 ]
  18. Doering W, Konig E, Sturm W: [Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)]. Z Kardiol. 1977 Mar;66(3):121-8. [857452 ]
  19. Kaplanski J, Weinhouse E, Topaz M, Genchik G: Verapamil and digoxin: interactions in the rat. Res Commun Chem Pathol Pharmacol. 1983 Dec;42(3):377-88. [6665298 ]
  20. Thompson DF, Carter JR: Drug-induced gynecomastia. Pharmacotherapy. 1993 Jan-Feb;13(1):37-45. [8094898 ]
  21. Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33. [15554746 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name:
CYP11A1
Uniprot ID:
P05108
Molecular weight:
60101.87
General function:
Involved in ATP binding
Specific function:
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
Gene Name:
ATP1A1
Uniprot ID:
P05023
Molecular weight:
112895.01

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular weight:
76448.0
General function:
Involved in transporter activity
Specific function:
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first step of the transport pathway of digoxin and various compounds into the urine in the kidney. May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells. This ion- transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation. May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg
Gene Name:
SLCO4C1
Uniprot ID:
Q6ZQN7
Molecular weight:
78947.5