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. 1975 May;54(1):65–74. doi: 10.1111/j.1476-5381.1975.tb07411.x

Cardiotonic steroids: correlation of sodium-potassium adenosine triphosphate inhibition and ion transport in vitro with inotropic activity and toxicity in dogs.

N A Beard, W Rouse, A R Somerville
PMCID: PMC1666382  PMID: 124610

Abstract

1. A new series of cardiotonics based on five steroid nuclei has been evaluated for inhibition of Na-+/K-+-ATPase and Rb uptake by red blood cells, and for inotropic activity and toxicity in dogs. Structure-activity relationships are discussed. 2. The in vitro tests can be used satisfactorily to predict inotropic activity, but not toxicity or therapeutic ratio. 3. Although compounds with greatly improved therapeutic ratios relative to ouabain and tolusin have been obtained, they proved to be strongly emetic in the conscious dog.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akera T., Larsen F. S., Brody T. M. The effect of ouabain on sodium- and potassium-activated adenosine triphosphatase from the hearts of several mammalian species. J Pharmacol Exp Ther. 1969 Nov;170(1):17–26. [PubMed] [Google Scholar]
  2. Bernstein J. C., Israel Y. Active transport of Rb86 in human red cells and rat brain slices. J Pharmacol Exp Ther. 1970 Aug;174(2):323–329. [PubMed] [Google Scholar]
  3. FRY D. L. Physiologic recording by modern instruments with particular reference to pressure recording. Physiol Rev. 1960 Oct;40:753–788. doi: 10.1152/physrev.1960.40.4.753. [DOI] [PubMed] [Google Scholar]
  4. Furnival C. M., Linden R. J., Snow H. M. Inotropic changes in the left ventricle: the effect of changes in heart rate, aortic pressure and end-diastolic pressure. J Physiol. 1970 Dec;211(2):359–387. doi: 10.1113/jphysiol.1970.sp009283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GLYNN I. M. THE ACTION OF CARDIAC GLYCOSIDES ON ION MOVEMENTS. Pharmacol Rev. 1964 Dec;16:381–407. [PubMed] [Google Scholar]
  6. Grahame-Smith D. G. Everest MS: Measurement of digoxin in plasma and its use in diagnosis of digoxin intoxication. Br Med J. 1969 Feb 1;1(5639):286–289. doi: 10.1136/bmj.1.5639.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haustein K. O., Markwardt F., Repke K. R. Different relationships between therapeutic and toxic actions of 16-epi-gitoxin, gitoxin and ouabain on isolated cardiac preparations. Eur J Pharmacol. 1970 Apr;10(1):1–10. doi: 10.1016/0014-2999(70)90150-0. [DOI] [PubMed] [Google Scholar]
  8. Hexum T., Samson F. E., Jr, Himes R. H. Kinetic studies of membrane (Na+-K+-Mg2+)-ATPase. Biochim Biophys Acta. 1970 Aug 15;212(2):322–331. doi: 10.1016/0005-2744(70)90213-5. [DOI] [PubMed] [Google Scholar]
  9. Kupchan S. M., Mokotoff M., Sandhu R. S., Hokin L. E. The chemistry and biological activity of derivatives of strophanthidin. J Med Chem. 1967 Nov;10(6):1025–1033. doi: 10.1021/jm00318a008. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Lee K. S., Klaus W. The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol Rev. 1971 Sep;23(3):193–261. [PubMed] [Google Scholar]
  12. Nakao T., Tashima Y., Nagano K., Nakao M. Highly specific sodium-potassium-activated adenosine triphosphatase from various tissues of rabbit. Biochem Biophys Res Commun. 1965 Jun 9;19(6):755–758. doi: 10.1016/0006-291x(65)90323-2. [DOI] [PubMed] [Google Scholar]
  13. PALMER R. F., NECHAY B. R. BIPHASIC RENAL EFFECTS OF OUABAIN IN THE CHICKEN: CORRELATION WITH A MICROSOMAL NA+-K+ STIMULATED ATP-ASE. J Pharmacol Exp Ther. 1964 Oct;146:92–98. [PubMed] [Google Scholar]
  14. Shigei T., Takeda K., Tashima Y., Nakao M. Relationship between the potentiation of potassium-induced contracture of cardiac muscle by four cardenolides and their inhibitory effects on the sodium potassium activated adenosine triphosphatase of brain. Experientia. 1971 Apr 15;27(4):415–416. doi: 10.1007/BF02137284. [DOI] [PubMed] [Google Scholar]
  15. Wilson W. E., Sivitz W. I., Hanna L. T. Inhibition of calf brain membranal sodium- and potassium-dependent adenosine triphosphatase by cardioactive sterols. A binding site model. Mol Pharmacol. 1970 Sep;6(5):449–459. [PubMed] [Google Scholar]

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