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Journal of Pharmacology And Experimental Therapeutics, Vol. 71, Issue 2, 114-125, 1941
Copyright © 1941 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON PURIFIED DIGITALIS GLUCOSIDES III. THE RELATIONSHIP BETWEEN THERAPEUTIC AND TOXIC POTENCY

McKEEN CATTELL 1 and HARRY GOLD 1

1 From the Department of Pharmacology, Cornell University Medical College, New York

The relative potency with regard to both therapeutic and toxic effects on isolated papillary muscles from the cat have been determined for the following glucosides: Ouabain (Merck), Digitoxin (Merck), Digitaline (Laboratoire Nativelle), Lanatoside A (Sandoz), Lanatoside B (Sandoz) and Lanatoside C (Cedilanid, Sandoz).

The minimum concentration of ouabain and digitoxin, i.e., that causing increased force of contraction in 50 per cent of experiments (therapeutic effect) is 1 part in 100 millions of Locke's solution; for the lanatoside compounds it is approximately 1 part in 10 millions.

When the concentration of any of the glucosides is sufficiently increased toxic effects are produced, including extra contractions, loss of excitability and diminished force of contraction.

The ratio of the concentrations producing therapeutic and toxic effects is the same for "Digitaline Nativelle" and ouabain. There is also similarity among the several lanatoside glucosides studied, and thus by this technic we have not been able to confirm the wide margin between the therapeutic and toxic dose reported by Moe and Visscher for lanatoside C.

Ouabain and "Digitaline Nativelle" both give a slightly higher value for the ratio of toxic to therapeutic concentration in comparison with the lanatoside compounds. The evaluation of the significance of this finding must await further evidence.

The available evidence pertaining to the questions of differences in the relationship between toxic and therapeutic doses among different glucosides is discussed, and the conclusion is reached that proof of the existence of such differences is still wanting.

Submitted on August 10, 1940




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