Mode of action of neuromuscular blocking agents / by W.D.M. Paton.

  • William Paton
Date:
[1956?]
Catalogue details

Licence: In copyright

Credit: Mode of action of neuromuscular blocking agents / by W.D.M. Paton. Source: Wellcome Collection.

    9/12 page 477
    1952) is related to potassium release into the intercellular spaces (Paton, 1952). It is worth noting, too, that the duration of elevation of plasma potassium consider¬ ably outlasts that of the endplate depolar¬ ization, and, a fortiori, that of the block itself. The attractive transience of suxa¬ methonium’s relaxant action may hide a more prolonged effect in the body as a whole. MIXED BLOCK We have discussed neuromuscular block so far in terms of two contrasted types: that by competition where the action of the transmitter is antagonized; and that by depolarization with the development of electrical inexcitability at the endplate, where a transmitter-like action is exerted but for an abnormal time. But there is evidence that neuromuscular block of an intermediate kind may exist, in which a depolarization may take place initially and pass off, leaving nevertheless a state of block, now competitive in character. Drugs which first stimulate and then desensitize the tissue both to their own action and to that of similar sub¬ stances have been known since Straub (1907) first showed the phenomenon for the action of muscarine on Aplysia heart. Nicotine, in its action on autonomic ganglia, is a notable example; and many sympathomimetics amines have the char¬ acteristic sequence of sympathomimetic followed by sympatholytic action. Among drugs active on the endplate a similar type of action is described for some of the aliphatic quaternary salts studied by Dallemagne and Phillipot (1951), Ginzel et al. (1952) and Zaimis (1953). With decyltrimethylammonium it has, indeed, been verified electrically that this drug will produce an endplate depolarization, which may then disappear, leaving a block of competitive type behind (Paton, 1951). But these observations are not on drugs in clinical use, and we must ask whether there is any possibility that the relaxants actually employed by the anaesthetist might come to behave in a similar way. Is it possible, in fact, that suxamethonium or decamethonium might come, perhaps under special conditions, to lose their characteristic action and resemble curare¬ like drugs? At present no decisive evi¬ dence exists. But there are several reasons which indicate, on pharmacological grounds, that such a development might occur. First, it is of interest to compare the structures of the compounds whose action is fairly well understood from the point of view of their lipophilic tendency. Data do not exist, and indeed are not easy to obtain, giving quantitative measurements of this sort. But one can estimate it in a simple way by enumerating the carbon atoms in each molecule (lipophilic) and comparing them (table II) with the number of quaternary groups (hydro¬ philic). One can then see how, with in¬ creasing proportions of hydrocarbon to hydrophilic material, the mode of action moves from depolarization through mixed action to pure competition. The point is, of course, one which Bovet (1951), in his classification of lepto- and pachycurares, has already taken up. But here I am trying to estimate, not the shape of the molecule, but its tendency to be fixed in a fatty or a watery phase—i.e., its partition coefficient. The scheme suggests that drugs with some measure of hydrocarbon loading may
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