Actions and clinical assessment of drugs which produce neuromuscular block / W.D.M. Paton and Eleanor J. Zaimis.

  • Paton, William D. M.
Date:
[1950?]
Catalogue details

Licence: In copyright

Credit: Actions and clinical assessment of drugs which produce neuromuscular block / W.D.M. Paton and Eleanor J. Zaimis. Source: Wellcome Collection.

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    Reprinted from The Lancet, November 18, 1950, p. 568 ACTIONS AND CLINICAL ASSESSMENT OF DRUGS WHICH PRODUCE NEUROMUSCULAR BLOCK W. D. M. Paton M.A., B.M. Oxfd MEMBER OE SCIENTIFIC STAFF, MEDICAL RESEARCH COUNCIL, AT THE NATIONAL INSTITUTE FOR MEDICAL RESEARCH Eleanor J. Zaimis M.D., B.Sc. Athens LECTURER IN DEPARTMENT OF PHARMACOLOGY, SCHOOL OF PHARMACY, UNIVERSITY OF LONDON That decamethonium may he used clinically to produce muscular relaxation in anaesthesia and in convulsion therapy, as suggested by us (Paton and Zaimis 1948a), is now well established (Organe 1949, Davies and Lewis 1949, Hobson and Prescott 1949, Hewer et al. 1949, Davies 1950). But it is clear from some reports that the fundamental differences in mechanism of action between decamethonium and drugs resembling d-tubocurarine are not sufficiently appreciated, and that this lack of under¬ standing may interfere with assessment of the value of such drugs. MODE OF ACTION OF DECAMETHONIUM AND d-TUBOCURARINE The fundamental action of decamethonium on skeletal muscle is a specific depolarisation of the muscle membrane at the motor end-plate (where the motor nerve-fibre ends on the muscle membrane) (Burns and Paton 1950). The first effect of this depolarisation, particularly if the decamethonium is injected rapidly into a muscle by an arterial route, is to excite a brief contraction. But the depolarisation then persists and spreads to adjacent regions of the muscle. Two further effects follow : (1) because the end-plate is already partly depolarised, a nerve impulse can no longer evoke so large an “ end- plate potential ” (the electrical response by which the muscle-fibre is excited) ; and (2) the surrounding depolarised area becomes electrically inexcitable, with the result that there is a zone of inexcitable muscle membrane 2-3 mm. in width between the point at which the end-plate potential is set up and the nearest normally excitable part of the muscle-fibre. The net result of the reduction of the end-plate potential, and of the inex¬ citability of the end-plate zone, is neuromuscular block. This action of decamethonium is analogous to that exerted by acetylcholine. Normally, in mammalian