Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin)

Abstract

Summary1. A titration assay with two end points is described for comparison of the emetic and lethal potencies of digitalis-like drugs. 2. A drug was infused at constant rate to a conscious, unrestrained cat. through an indwelling venous cannula. At the moment of vomiting the cat was rapidly anaesthetized and infusion continued at the same rate until the moment of cardiac arrest. 3. With very slow and very fast infusions, the emetic and lethal doses tended to rise. In the range between these extremes (which varied from drug to drug) they were independent of time. 4. The observations could be accounted for by analogue computation, assuming that the drugs entered an initial pool and were distributed at finite rates to receptors in the CNS (vomiting centre) and heart. 5. Half times of metabolic loss derived from this computation for digitoxin, digoxin and ouabain (17, 9 9 and 1-8 h, respectively) were in the same ratio as the threefold longer half times reported for these drugs in man. 6. When measured with infusion rates in the time independent range, the ratio of lethal to emetic doses did not vary between the drugs studied. All caused vomiting at 40% of the lethal dose. 7. From a review of the literature, the emetic and cardiotoxic actions of digitalis-like drugs appear inseparable and probably share a common biochemical mechanism. 8. It is concluded that foreseeable improvements in digitalis-like drugs are small and would depend on the elimination of any local emetic effect on gut receptors which they may have.

Phenotypic diversity, mimicry and natural selection in the African butterfly Hypolimnas misippus L. (Lepidoptera: Nymphalidae)

“…They conclude that only 6% of the butterflies are likely to prove emetic to this bird. However, they fail to point out either that different cardenolides, which they did not characterize, vary greatly in their level of pharmacological activity (Parsons & Summers, 1971) or that cardenolide levels well below those causing emesis may, nevertheless, confer sufficient inedibility upon the butterflies to be an efficient deterrent to predators.…”

Relative Selectivity of Plant Cardenolides for Na+/K+-ATPases From the Monarch Butterfly and Non-resistant Insects

“…Duffey (1977) stated that while non-polar cardenolides are absorbed more easily via the gut relatively more polar cardenolides seem to cause emesis in vertebrates at lower doses. While the moderately non-polar cardenolides calactin and calotropin are easily absorbed across the gut they also have low-dose requirements to cause emesis after reaching the blood stream of a vertebrate (see also Parsons and Summers, 1971 ). Thus, calactin and calotropin seem to represent the ideal substrate for sequestration, which is supported by observations on the grasshopper Poekilocerus bufonius that also selectively sequesters calactin and calotropin ( Roeske et al, 1976 ).…”

Cardenolide storage inDanaus chrysippus(L.) with additional notes onD. plexippus(L.)

“…The results were the same: no emesis followed. I t is well known th at different digitalis-like substances show differences in activity (Parsons & Summers 1971) and it is possible th a t the absence of calactin in these two species of Lepidoptera accounts for their lack of emetic qualities. On the other hand Parsons did not feed pupae to his birds and therefore the two series of experiments are not strictly comparable.…”