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.

    4/16 page 350
    excitability of the end-plate region is actually increased, and then it passes over (in a time depending on the dose of decamethonium) into a depression of excitability. This inexcitability can be demonstrated in another way: by exciting the muscle directly to one side of the end-plate region and re¬ cording action potentials either side of the end plate. In a completely curarized muscle, propagation of such action potentials proceeds along the full length of muscle fiber, crossing the end-plate region without alteration. With decamethonium, however, the end plate now represents a region of block across which the action potential is unable to excite the muscle mem¬ brane beyond. This evidence shows that the depolarization of the end plate leads to an inexcitability of the end-plate region adequate to cause neuromuscular block. We found, in addition, that block, for a given degree of depolariza¬ tion, was greater the longer the depolarization had lasted. This naturally follows from the spread of depolarization and of inexcitability, which will create, with lapse of time, a widening barrier of inexcitable tissue between the end plate and normal muscle. There is some evidence, however, that another mechanism may also be involved. Particularly after a large dose of decamethonium, it seems probable that the drug reduces the end-plate potential by diminishing the remaining possible depolarization. Since the end plate is already well de¬ polarized, further discharge of acetylcholine on to the end plate can only elicit a small electrical response. We have, therefore, two mechanisms by which the depolarization evoked by decamethonium can block neuromuscular excitation: the development of electrical inexcitability of the membrane, and a reduction of the end-plate potential by reason of the already existing end-plate depolarization. It might be argued, however, that these processes were merely subsidiary to some other form of neuromuscular block. Although there is no evidence at all to support such an idea, the experiments quoted do not completely exclude it. One can bring against it additional experiments of another kind, however, in which polarizing currents are applied to the end-plate region. As is well known, if a curarized end-plate region is depolarized by applying a cathode to it, transmission returns. Conversely, making the end plate of a curarized muscle positive, by applying an anode, deepens the failure of transmission. If a muscle under decamethonium is tested in the same way, however, one obtains precisely the opposite results. Transmis¬ sion is promptly restored with an anode; a cathode merely serves to deepen it. There seems no conceivable way in which this result could come about, unless the depolarization of the end plate was actually causing the block. It seems inescapable, therefore, that the depolarization is not incidental to a normal, true curare-like action, but that it is actually responsible for the blocking action of decamethonium. Evidence of the same kind has been obtained for the block obtained with acetylcholine, when given either in large doses or in the presence of anti¬ cholinesterases. One obtains a depolarization of the end plate which is in-
    digitised image 1
    digitised image 2
    digitised image 3