Digitoxin
Digitoxin is only found in individuals that have used or taken this drug. It is a cardiac glycoside sometimes used in place of digoxin. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665)Digitoxin inhibits the Na-K-ATPase membrane pump, resliting in an increase in intracellliar sodium and calcium concentrations. Increased intracellliar concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
MOLSDFPDBSMILESInChI
Structure for HMDB15468 (Digitoxin)
C41H64O13
764.9391
764.434692134
4-[(1S,2S,5S,7R,10R,11S,14R,15R)-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-hydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]-2,5-dihydrofuran-2-one
digitoxin
71-63-6
[H][C@]12CC[C@]3([H])[C@]([H])(CC[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=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
WDJUZGPOPHTGOT-XUDUSOBPSA-N
This 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.
Organic compounds
Lipids and lipid-like moleclies
Steroids and steroid derivatives
Steroid lactones
Cardenolide glycosides and derivatives
Aliphatic heteropolycyclic compounds
Expected but not Quantified
Solid
LC-MS/MS Spectrum – Linear Ion Trap , positivesplash10-052f-0000037900-5f2fccb009b7c0b1dafeView in MoNA
LC-MS/MS Spectrum – Linear Ion Trap , positivesplash10-052f-0000038900-a997014628166d650039View in MoNA
Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available
Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available
Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available
Mass Spectrum (Electron Ionization)splash10-052g-9620000000-5ddc0df4702d2f0b8581View in MoNA
13C NMR SpectrumNot Available
Not Available
Not Available
Not Available
None
None
DB01396
Not Available
Not Available
Not Available
Not Available
Not Available
389987
C06955
Not Available
Not Available
Digitoxin
HMDB15468
HMDB15468
Not Available
441207
Not Available
28544
- Kurowski V, Iven H, Djonlagic H: Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies. Intensive Care Med. 1992;18(7):439-42. [PubMed:1469187 ]
- Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P: Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anticancer Drugs. 2001 Jun;12(5):475-83. [PubMed:11395576 ]
- Hippius M, Humaid B, Sicker T, Hoffmann A, Gottler M, Hasford J: Adverse drug reaction monitoring–digitoxin overdosage in the elderly. Int J Clin Pharmacol Ther. 2001 Aug;39(8):336-43. [PubMed:11515708 ]
- Belz GG, Breithaupt-Grogler K, Osowski U: Treatment of congestive heart failure–current status of use of digitoxin. Eur J Clin Invest. 2001;31 Suppl 2:10-7. [PubMed:11525233 ]
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
References
- Wang SW, Lin H, Hwang JJ, Wang PS: Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells. J Cell Biochem. 1999 Jul 1;74(1):74-80. [PubMed:10381263 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- 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
References
- Chen JJ, Wang PS, Chien EJ, Wang SW: Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells. Br J Pharmacol. 2001 Apr;132(8):1761-8. [PubMed:11309248 ]
- Marcus FI, Ryan JN, Stafford MG: The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay. J Lab Clin Med. 1975 Apr;85(4):610-20. [PubMed:123547 ]
- Prignitz R, Frohlich D, Hoffmeister G: [Influence of roentgen rays on electrolyte changes and metabolism of the myocardium. VII. Radiation-induced inhibition of the sodium- and potassium–activated microscomal-trasport ATPase]. Strahlentherapie. 1976 Apr;151(4):356-65. [PubMed:131389 ]
- Bluschke V, Bonn R, Greeff K: Increase in the (Na+ + K+)-ATPase activity in heart muscle after chronic treatment with digitoxin or potassium deficient diet. Eur J Pharmacol. 1976 May;37(1):189-91. [PubMed:132355 ]
- Fricke U: [New aspects on the mode of action of cardiac glycosides]. Fortschr Med. 1976 Nov 11;94(32):1037-45. [PubMed:136410 ]
- Hauck C, Potter T, Bartz M, Wittwer T, Wahlers T, Mehlhorn U, Scheiner-Bobis G, McDonough AA, Bloch W, Schwinger RH, Muller-Ehmsen J: Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase alpha1beta1, alpha2beta1 and alpha3beta1. Eur J Pharmacol. 2009 Nov 10;622(1-3):7-14. doi: 10.1016/j.ejphar.2009.08.039. Epub 2009 Sep 12. [PubMed:19751721 ]
Transporters
- General function:
- Involved in ATP binding
- Specific function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular weight:
- 141477.3
References
- Pauli-Magnus C, Murdter T, Godel A, Mettang T, Eichelbaum M, Klotz U, Fromm MF: P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin. Naunyn Schmiedebergs Arch Pharmacol. 2001 Mar;363(3):337-43. [PubMed:11284449 ]
- General function:
- Involved in transporter activity
- Specific function:
- Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids
- Gene Name:
- SLCO1A2
- Uniprot ID:
- P46721
- Molecular weight:
- 74144.1
References
- Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [PubMed:8786566 ]
- 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
References
- 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. [PubMed:14993604 ]