The pharmacology of the toxiferines / by W.D.M. Paton and W.L.M. Perry.

  • William Paton
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: The pharmacology of the toxiferines / by W.D.M. Paton and W.L.M. Perry. Source: Wellcome Collection.

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    seen beating through the thoracic wall. The whole gamut from the beginning of muscular weakness to complete paralysis was covered roughly by a 100 per cent increase in dose, both with the toxiferines and with d-tubocurarine. There was a definite difference in the duration of paralysis ; the paralysis by d-tubocurarine was more rapid in onset and passed off more quickly than that due to the three most potent toxiferines. We also found (Table I) that, whereas the potency of the toxiferines remains remarkably constant at different times of year, the absolute potency of J-tubocurarine varies considerably. It is this latter factor which is mainly responsible for the large swings in the relative potency of the toxiferines with respect to ^/-tubocurarine which were observed in the different assays. It is known that there are many physiological differences between summer and winter frogs which, no doubt, account for the seasonal variations in the potency of J-tubocurarine. The relative constancy of the ED50’s of the toxiferines for frogs at all seasons may be related to their remarkable constancy of potency in different species, described later. Potency in other species.-—In view of the very high potency of toxiferine I in the frog, together with the fact that our supply of this compound was relatively abundant, it was possible to extend our observations on its potency to other animal species. Table II summarizes the results of these experiments. The most striking TABLE II ACTIVITY OF TOXIFERINE I IN DIFFERENT SPECIES Species ED50 pg./kg. Potency X d.t.c. Frog (March) 7.5 240 Frog (October) 14 76 Mouse (righting reflex) 10 12 Rabbit (head-drop) .. 11 20 Cat (tibialis twitch) .. 15-20 15 fact about these observations is the similarity in the effective doses of toxiferine I, whether tested in frog, mouse, rabbit, or cat, the range of variation being no more than that among frogs at different seasons. The difference between the effective doses of d-tubocurarine for mammals and frogs presents a marked contrast. In all species investigated, as in the frog, the onset of paralysis is slower and the duration of paralysis longer with the toxiferines than with d-tubocurarine. For instance, in the cat after an intravenous dose, the presence of toxiferine I is demon¬ strable two hours, or sometimes even three hours, later by the increased sensitivity of the animal to a further dose ; and the period of actual paralysis is correspondingly longer than with J-tubocurarine. Mechanism of muscular paralysis.—Although there could be little doubt that toxiferines, being the active principles of calabash curare, exerted their paralysing action by blocking transmission at the myoneural synapse, we thought it important to establish this for certain. To do this, it was necessary to show that the toxiferines affected neither muscle nor nerve directly. We found that there was no effect on
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