Anticholinesterases / W.D.M. Paton.

  • William Paton
Date:
[1954?]
Catalogue details

Licence: In copyright

Credit: Anticholinesterases / W.D.M. Paton. Source: Wellcome Collection.

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    other actions in addition to antiesterase effects, which have complicated this sort of progress. Fifth, it must be mentioned that the phosphorus compounds do not only inhibit cholin¬ esterases but also some other enzymes, the so-called aliesterase, the proteolytic enzyme chymotrypsin, and the B-type esterase of mammalian sera (Mendel, Myers, et al., 1953). Our simple picture, therefore, of reversible specific inhibitors chemically related to acetylcholine can well be retained, pro¬ vided we remember the two types of attachment to the enzyme, and allow for a combination of inhibitor with receptor which is at least so slowly reversible as to be, for practical purposes, permanent. There are, however, important complications: most inhibitors are pretty active against both enzymes, a few much more against one than the other; and cholinesterase is not the only type of enzyme inhibited. There is one inhibitor of cholinesterase particularly active against pseudo-esterase, which comes in a category by itself, viz. triorthocresylphosphate (TOCP). This has been known for some years to produce a central nervous paralysis; it was later found to be an inhibitor of cholinesterase and later still found to be particularly active against pseudo-cholinesterase in the brain (Earl and Thompson, 1952). The interest in it arises from the fact that it produces central nervous system lesions of a kind also seen with two of the anticholinesterases, which will be discussed later. Effects of Inhibition of Cholinesterase It is fairly straightforward to interpret most of the effects seen in the terms of our original simple picture as being due to accu¬ mulation of acetylcholine, so that the results of inhibiting cholinesterases in the body provide a concise exercise in the anatomy of cholinergic nerves. The careful studies by Harvey and his colleagues on the effect of DFP on man, still provide one of the best descriptions of these effects. (Table 1.) The most prominent effects are the muscarinic ones. Of the nicotinic actions of acetylcholine only that on striated muscle reveals itself at all obviously. Remaining is a group of central nervous system actions, some of a quite remarkable kind. There has been a good deal of discussion as to whether the
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