The pharmacology of decamethonium / by W.D.M. Paton.

  • Paton, William D. M.
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: The pharmacology of decamethonium / by W.D.M. Paton. Source: Wellcome Collection.

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    Made in United States of America Reprinted from Annals of The New York Academy of Science Vol. 54, Art. 3, Pages 347-361, 1951 THE PHARMACOLOGY OF DECAMETHONIUM By W. D. M. Paton National Institute for Medical Research, Mill Hill, London, N.W. 7 The main features of the pharmacology of decamethonium are already well known,20’ 5 and there is no need to review these here in detail or to comment on its remarkable specificity of action. The recent analysis, however, by Burns and myself,3 of the action of decamethonium at the end plate, throws considerable light on the numerous contrasts which have emerged, from the earliest experiments onwards, between decamethonium and those other substances causing neuromuscular block (of which I shall take d-tubocurarine as representative). In this paper, therefore, these differences will first be critically reviewed, and then related to the modes of action of the two drugs. The Differences between Decamethonium and d-Tubocurarine. In table 1 are tabulated the responses observed under different conditions with the two compounds. They fall naturally into several groups. First are the differences in the incidence of effect on different muscles. These appear not only between species (for instance, compare the rat and the cat), but also within species, as our results with the soleus and tibialis of the cat showed.20’22 It seems that even in man the same thing appears, in that decamethonium affects the pharyngeal, laryngeal, facial, and sometimes respiratory muscles less intensely in relation to the muscles of the trunk than does d-tubocurarine, and the muscles of the hand may also differ in their relative sensitivity to the two agents.7,11 •16•21 *26 These differences in muscle sensitivity are confusing and are still completely unexplained. There is, however, one general feature about them. This is the inverse relation¬ ship between sensitivity to decamethonium and sensitivity to d-tubocurarine. Thus, the rat is more sensitive than the cat to the latter, but much less sensitive than the cat to decamethonium. Soleus and tibialis in the cat show the same relationship. Even in man, the exceptional sensitivity of ocular and pharyngeal muscles to d-tubocurarine, relative to the other muscles, is less when the paralysis is induced with decamethonium. One can put the case in general terms. If the ratio “sensitivity of muscle a/sensitivity of muscle b” is, with d-tubocurarine, raised above unity, then decamethonium will reduce it, often to far less than unity. Taking the cases already quoted, the ratio, “rat sensitivity/cat sensitivity,” is 2 for d-tubocurarine and 0.005 for decamethonium, and that for “cat soleus/cat tibialis” is roughly 1.6 for d-tubocurarine and 0.7 for decamethonium. It is unlikely that this inverse relation holds invariably. I know of no excep¬ tion to it so far, however, and it helps to introduce some order into the observations. Further, as we shall see, something of the sort would be expected from the contrasting ways in which the two compounds produce their effects. Second, we may take the effect of substances which raise the end-plate threshold to acetylcholine. Here again, we have the same inverse relation,