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

  • William Paton
Date:
[1951?]
Catalogue details

Licence: In copyright

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

    14/16 page 360
    Doctor Lawrence Stark (New York Medical College, New York, N. Y.): We have been working in Professor Brown’s laboratory at the University College, London, on end-plate potentials from the frog sciatic-sartorius preparation. Using acetylcholine and prostigmine, we blocked neuromus¬ cular conduction by depolarization, a mechanism similar to that described by Doctor Paton for decamethonium. We also noted the localization of depolarization to the anatomical end-plate region. With reference to Doctor Jarcho’s data on fibrillation of denervated muscle, I think it is important to remember that less is known about de¬ nervated muscle than about the usual nerve-muscle preparations. One should therefore not try to reason facilely from evidence concerning fibrilla¬ tion to mechanisms of drug action. These fibrillations are occurring spon¬ taneously—perhaps they are another sort of biological noise—and, presum¬ ably, no evidence for their origin from nerve endings is available. Thus, neuro-muscular transmission might not be directly involved in their pro¬ duction. Doctor Paton: First, as to Dr. Acheson’s points. I am afraid I wasn’t sufficiently explicit in explaining the diagram of excitability around the end-plate region exposed to decamethonium. The ordinates were the volt¬ age required to produce, by direct electrical excitation of the muscle at various points along it, an action potential of constant size recorded at the tip of the muscle. Thus, the muscle response was held constant. His remarks about the use of the term “threshold” are entirely justified and acceptable. I wish I saw more clearly how the action of decamethon¬ ium was related to accommodation and adaptive phenomena. I think it is quite likely that in time a great number of these will ultimately all be explicable in terms of the properties of cathodal block. At the moment, however, we are a long way from being able to draw any general picture of this sort. Doctor Lilienthal said some nice things about the wrork I reported. I should like to say in reply, as I could not in the paper, how much it owes to other people, particularly to my recent colleagues at Hampstead, G. L. Brown, F. C. Macintosh, and Doctor Harold King, and to many people here both on the platform and off it. I am very conscious of the impor¬ tance of the muscle and species variation, as raised by Doctor Lilienthal. I still think that the cat is the best animal to use, particularly since using it to predict the dose of decamethonium to be used in our first human trials turned out so successfully. Finally, on the question of nomenclature of pharmacological effects— Sir Henry Dale’s advice was extremely shrewd. I don’t believe, however, that giving the name of a drug to an action entirely removes any supposition as to the method of its action, and it may introduce difficulties of its own. These are particularly wTell illustrated by the term “nicotine-like.” We know that this action has at least four independent aspects: end-plate stim¬ ulation, neuromuscular block by competition with acetylcholine, ganglion stimulation, and ganglionic block, epitomized respectively by decamethon-
    digitised image 1
    digitised image 2
    digitised image 3