Skip to main content
PMC home page
British Journal of Pharmacology and Chemotherapy logoLink to British Journal of Pharmacology and Chemotherapy
. 1962 Apr;18(2):311–324. doi: 10.1111/j.1476-5381.1962.tb01411.x

Chemical structure and pharmacological activity of some derivatives of digitoxigenin and digoxigenin

B T Brown, Anne Stafford, S E Wright
PMCID: PMC1482116  PMID: 13873586

Abstract

A series of derivatives of digitoxigenin and digoxigenin were prepared and tested for toxicity in the cat and the guinea-pig and on the isolated heart of the 48-hr chick embryo, and for inotropic activity on the cat isolated papillary muscle and the guinea-pig Langendorff heart. The order of relative potency of the compounds remained the same whether they were tested for toxicity or for positive inotropic activity. There are three molecular centres in the cardiac aglycone that are linked closely with cardiac activity. These are: (a) an OH at carbon-3 which can be combined as a glycoside, thus enhancing activity, or esterified or oxidized, producing compounds of lower activity; the maximum intensity of the inotropic response was reduced in the less potent compounds; (b) a 14-β-OH associated with a cis C-D ring junction, alteration of which abolished activity; (c) an unsaturated cyclobutenolide ring which cannot be reduced without a great decrease in activity.

Full text

PDF
311

Selected References

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

  1. ASHLEY J. J., BROWN B. T., OKITA G. T., WRIGHT S. E. The metabolites of cardiac glycosides in human urine. J Biol Chem. 1958 May;232(1):315–322. [PubMed] [Google Scholar]
  2. BROWN B. T., RANGER D., WRIGHT S. E. The excretory products of lanatoside C and digitoxin in the rat. J Pharmacol Exp Ther. 1955 Mar;113(3):353–358. [PubMed] [Google Scholar]
  3. CHEN K. K., HENDERSON F. G., ANDERSON R. C. Comparison of forty-two cardiac glycosides and aglycones. J Pharmacol Exp Ther. 1951 Dec;103(4):420–430. [PubMed] [Google Scholar]
  4. CHEN K. K., HENDERSON F. G., ANDERSON R. C. The cardiac action of Helleborus glycosides and their aglycones. J Pharmacol Exp Ther. 1950 Aug;99(41):325–400. [PubMed] [Google Scholar]
  5. CHEN K. K., HENDERSON F. G. Pharmacology of sixty-four cardiac glycosides and aglycones. J Pharmacol Exp Ther. 1954 Jul;111(3):365–383. [PubMed] [Google Scholar]
  6. CREESE R. Bicarbonate ion and striated muscle. J Physiol. 1949 Dec;110(3-4):450–457. doi: 10.1113/jphysiol.1949.sp004452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. RAND M., STAFFORD A. Effect of the rate of elimination of digoxigenin in the guinea pig on the determination of its lethal dose. Nature. 1959 Mar 7;183(4662):688–689. doi: 10.1038/183688a0. [DOI] [PubMed] [Google Scholar]
  8. REPKE K., KLESCZEWSKI S., ROTH L. [On splitting and hydroxylation of digitoxin in the rat]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1959;237:34–48. [PubMed] [Google Scholar]
  9. TANZ R. D., KERBY C. F. The inotropic action of certain steroids upon isolated cardiac tissue; with comments on steroidal cardiotonic structure-activity relationships. J Pharmacol Exp Ther. 1961 Jan;131:56–64. [PubMed] [Google Scholar]
  10. VICK R. L., KAHN J. B., Jr, ACHESON G. H. Effects of dihydro-ouabain, dihydrodigoxin and dihydrodigitoxin on the heart-lung preparation of the dog. J Pharmacol Exp Ther. 1957 Nov;121(3):330–339. [PubMed] [Google Scholar]
  11. WALTON R. P., GAZES P. C. The effect of digitalis and other drugs on heart contractile force: clinical implications. South Med J. 1951 May;44(5):418–423. doi: 10.1097/00007611-195105000-00009. [DOI] [PubMed] [Google Scholar]
  12. WOLLENBERGER A. Non-specificity of the effect of cardiac glycosides on the polymerization of actin. Experientia. 1954 Jul 15;10(7):311–312. doi: 10.1007/BF02158746. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology and Chemotherapy are provided here courtesy of The British Pharmacological Society

RESOURCES