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Chemical Compound Review

AC1NWALC     4-[(3S,5R,10S,13R,14S,17S)-3- [(2R,4S,5S...

Synonyms: BSPBio_002205, KBioGR_001087, KBioSS_001444, CCG-38362, NINDS_000036, ...
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Disease relevance of digitoxin


Psychiatry related information on digitoxin


High impact information on digitoxin

  • Sarafotoxins, a group of 21-residue cardiotoxic peptides from snake venom that induce coronary vasoconstriction, show high-affinity binding to rat atrial and brain membranes and activate the hydrolysis of phosphoinositides [10].
  • Amoxapine overdose. Coma and seizures without cardiotoxic effects [11].
  • Less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer [12].
  • Underlying pathogenetic mechanisms may include free-radical-mediated myocyte damage, adrenergic dysfunction, intracellular calcium overload, and the release of cardiotoxic cytokines [13].
  • HERG is likely to be the primary target for the known cardiotoxic effects of other, related antihistamines [14].

Chemical compound and disease context of digitoxin


Biological context of digitoxin


Anatomical context of digitoxin


Associations of digitoxin with other chemical compounds


Gene context of digitoxin

  • In the present study, we assessed the hypothesis that cardiotoxic effects of proinflammatory cytokines are mediated by the activation of NF-kappaB [35].
  • Previous in vivo data show a markedly enhanced cardiotoxic response to doxorubicin in beta2-/- mice, which is rescued by the additional deletion of the beta1-AR [36].
  • In conclusion, the differential cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role [36].
  • In healthy human subjects and in patients with atherosclerotic vascular diseases, the effect of COX-2 inhibition on coagulation is equally unclear as no prospective, randomized, double-blinded studies sufficiently powered to investigate cardiovascular endpoints have been performed to directly investigate a potentially cardiotoxic effect of coxibs [37].
  • This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline administration [38].

Analytical, diagnostic and therapeutic context of digitoxin

  • In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts [39].
  • CONCLUSION: RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy [40].
  • PURPOSE: We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers, Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer [41].
  • Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment [42].
  • They also were less cardiotoxic in cell culture [43].


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  11. Amoxapine overdose. Coma and seizures without cardiotoxic effects. Kulig, K., Rumack, B.H., Sullivan, J.B., Brandt, H., Spyker, D.A., Duffy, J.P., Shipe, J.R. JAMA (1982) [Pubmed]
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  15. Mitochondrial toxin 3-nitropropionic acid induces cardiac and neurotoxicity differentially in mice. Gabrielson, K.L., Hogue, B.A., Bohr, V.A., Cardounel, A.J., Nakajima, W., Kofler, J., Zweier, J.L., Rodriguez, E.R., Martin, L.J., de Souza-Pinto, N.C., Bressler, J. Am. J. Pathol. (2001) [Pubmed]
  16. Differences in steady-state inactivation between Na channel isoforms affect local anesthetic binding affinity. Wright, S.N., Wang, S.Y., Kallen, R.G., Wang, G.K. Biophys. J. (1997) [Pubmed]
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  19. Effects of alpha-adrenoceptor agonists and antagonists on ouabain-induced arrhythmias and cardiac arrest in guinea-pig. Thomas, G.P., Tripathi, R.M. Br. J. Pharmacol. (1986) [Pubmed]
  20. Cardiotoxicity and comparative pharmacokinetics of six anthracyclines in the rabbit. Jaenke, R.S., Deprez-DeCampeneere, D., Trouet, A. Cancer Res. (1980) [Pubmed]
  21. Molecular mechanisms of doxorubicin-induced cardiomyopathy. Selective suppression of Reiske iron-sulfur protein, ADP/ATP translocase, and phosphofructokinase genes is associated with ATP depletion in rat cardiomyocytes. Jeyaseelan, R., Poizat, C., Wu, H.Y., Kedes, L. J. Biol. Chem. (1997) [Pubmed]
  22. Human ether-a-go-go-related (HERG) gene and ATP-sensitive potassium channels as targets for adverse drug effects. Zünkler, B.J. Pharmacol. Ther. (2006) [Pubmed]
  23. New insights into the second generation antihistamines. Walsh, G.M., Annunziato, L., Frossard, N., Knol, K., Levander, S., Nicolas, J.M., Taglialatela, M., Tharp, M.D., Tillement, J.P., Timmerman, H. Drugs (2001) [Pubmed]
  24. Clinical decision making based on radionuclide determined ejection fraction in oncology patients. Peng, N.J., Advani, R., Kopiwoda, S., Fisher, G., Strauss, H.W. J. Nucl. Med. (1997) [Pubmed]
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  27. Analyses of the molecular mechanism of adriamycin-induced cardiotoxicity. Gille, L., Nohl, H. Free Radic. Biol. Med. (1997) [Pubmed]
  28. Biochemical and pharmacological properties of a cardiotoxic factor isolated from the blood serum of burned patients. Moati, F., Sepulchre, C., Miskulin, M., Huisman, O., Moczar, E., Robert, A.M., Monteil, R., Guilbaud, J. J. Pathol. (1979) [Pubmed]
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  30. Role of (+-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) in modulating free radical scavenging enzymes in doxorubicin-induced cardiomyopathy. Alderton, P., Gross, J., Green, M.D. Cancer Res. (1990) [Pubmed]
  31. Clinical and pharmacologic study of the epirubicin and paclitaxel combination in women with metastatic breast cancer. Grasselli, G., Viganò, L., Capri, G., Locatelli, A., Tarenzi, E., Spreafico, C., Bertuzzi, A., Giani, A., Materazzo, C., Cresta, S., Perotti, A., Valagussa, P., Gianni, L. J. Clin. Oncol. (2001) [Pubmed]
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  34. Effects of ouabain on technetium-99m-Q12 and thallium-201 extraction and retention by isolated rat heart. McGoron, A.J., Gerson, M.C., Biniakiewicz, D.S., Washburn, L.C., Millard, R.W. J. Nucl. Med. (1996) [Pubmed]
  35. Blockade of NF-kappaB improves cardiac function and survival without affecting inflammation in TNF-alpha-induced cardiomyopathy. Kawamura, N., Kubota, T., Kawano, S., Monden, Y., Feldman, A.M., Tsutsui, H., Takeshita, A., Sunagawa, K. Cardiovasc. Res. (2005) [Pubmed]
  36. Differential cardiotoxic/cardioprotective effects of beta-adrenergic receptor subtypes in myocytes and fibroblasts in doxorubicin cardiomyopathy. Fajardo, G., Zhao, M., Powers, J., Bernstein, D. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  37. Cyclooxygenase-2 inhibition and coagulation. Steffel, J., Lüscher, T.F., Ruschitzka, F., Tanner, F.C. J. Cardiovasc. Pharmacol. (2006) [Pubmed]
  38. Anthracycline cardiotoxicity in transgenic mice overexpressing SR Ca2+-ATPase. Burke, B.E., Olson, R.D., Cusack, B.J., Gambliel, H.A., Dillmann, W.H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  39. Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia. Ronson, R.S., Thourani, V.H., Ma, X.L., Katzmark, S.L., Han, D., Zhao, Z.Q., Nakamura, M., Guyton, R.A., Vinten-Johansen, J. Circulation (1999) [Pubmed]
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  42. Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin. van Acker, S.A., Boven, E., Kuiper, K., van den Berg, D.J., Grimbergen, J.A., Kramer, K., Bast, A., van der Vijgh, W.J. Clin. Cancer Res. (1997) [Pubmed]
  43. 6- and 7-substituted 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H-dibenz[de,h] isoquinoline-1,3-diones: synthesis, nucleophilic displacements, antitumor activity, and quantitative structure-activity relationships. Sami, S.M., Dorr, R.T., Sòlyom, A.M., Alberts, D.S., Iyengar, B.S., Remers, W.A. J. Med. Chem. (1996) [Pubmed]
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