The pharmacology of ganglion blocking agents / by W.D.M. Paton.

  • William Paton
Date:
[1959?]
Catalogue details

Licence: In copyright

Credit: The pharmacology of ganglion blocking agents / by W.D.M. Paton. Source: Wellcome Collection.

    2/12 page 366
    practice; so much so, that no effect achieved by them should be interpreted in terms other than those of ganglion block. From time to time, peculiar reactions are observed and then additional properties are proposed, on the heart, on skeletal muscle or centrally; but if, on the one hand, one fully ap¬ preciates the pharmacologic evidence, and on the other, one views such reactions critically, I doubt that it is ever necessary to be driven to any other than ganglionic considerations, even when discussing such obscure problems as the pulmonary changes occasionally seen in treated malignant hyper¬ tension.11 THE PROPERTIES OF MECAMYLAMINE AND PEMPIDINE The position is somewhat different when one turns to the newer ganglion blocking agents, of which mecamylamine and pempidine are of greatest in¬ terest at the moment. Mecamylamine is a secondary amine and pempidine a tertiary amine. They are alike in their dissociation constants and not widely dissimilar in molecular weights. The fact that they can, exist, although only to a small degree, in the un-ionized form, transforms their characteristics.1, 4’ 6, 7, 9, 14, 19 1. As is well known, they are active by mouth because they are, for prac¬ tical purposes, completely absorbed. For accuracy’s sake perhaps one should say that the absorption may not be strictly complete but certainly 50 per cent or better. This probably compares well with any other medicament given by mouth and means that, even if absorption varies, the proportion of the intended dose taken in cannot vary by more than a factor of two, and normally will vary much less. 2. At the same time, their fate in the body is much modified by their in¬ tracellular passage, for it is clear that many tissues, especiallv spleen, liver and lung and other tissues rich in nuclei, can take up mecamylamine and pempidine. 3. Thirdly, the renal handling of these compounds is changed. One might have wondered whether they would be treated like tetraethylammonium bv being actively secreted by the tubules. It emerges, on the contrary, that the un-ionized form of these compounds is reabsorbed from the tubules. The rate of reabsorption, of course, depends on the amount un-ionized, hence the greater excretion when the urine is acid and the greater reabsorption when the urine is alkaline. This has offered the rather attractive idea of controlling duration of action by controlling the pH of the urine. However, other factors controlling duration of action, which do not depend on urinary pH, are also very important, so that the scope for control in this way is somewhat limited. The practical significance, perhaps, is rather that under conditions when the urinary pH may change, variations in apparent potency or in duration of action of these drugs must be anticipated. 4. Lastly, with mecamylamine and pempidine the possibility of central actions must be canvassed. There does not appear to have been much analytic work on this aspect, and indeed it would not be a very easy study. But it is sufficiently clear from the clinical reports that mecamylamine at least can have central effects leading to confusional states, tremor, mania and the like.
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