The effects of muscle relaxants other than muscular relaxation / W.D.M. Paton.

  • Paton, William D. M
Date:
[1959?]
Catalogue details

Licence: In copyright

Credit: The effects of muscle relaxants other than muscular relaxation / W.D.M. Paton. Source: Wellcome Collection.

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    Reprinted from Anesthesiology, Vol. 20, No. 4, July-August, 1959 Printed in U. S. A. THE EFFECTS OF MUSCLE RELAXANTS OTHER THAN MUSCULAR RELAXATION W. D. M. Paton, D.M, F.R.S. A muscle relaxant may effect actions other than simple neuromuscular block in at least three ways. First, the depolarizing stimulant drugs display an excitatory stage as an in¬ trinsic element in the development of the block, from which may flow additional actions. Second, the relaxants owe their activity to a chemical relationship to acetylcholine; if they are able to compete with or imitate acetylcho¬ line at one synapse then they are liable to have activity at some other cholinergic synapse, or to react in some way with the enzymes which destroy acetylcholine. Third, the muscle re¬ laxants in general use are all basic compounds, and hence need to be scrutinized for a number of reactions liable to occur, sometimes rather nonspecifically, among organic bases. These three headings will be discussed first; finally, the problem of the assessment of such additional actions will be briefly treated. A number of special references will be given; others will be found in the valuable monograph on muscle relaxants by Foldes.1 The Consequences of End-plate Depolarization Muscle Pains. It was early recognized that the first action of decamethonium or succinyl- choline (suxamethonium) is to augment the response of a muscle to excitation of its motor nerve (by rendering the response to a single nerve volley repetitive), and to elicit inco¬ ordinate fasciculations in a muscle, independ¬ ent of nervous excitation, and present after section of the nerve trunk.2 These fascicula¬ tions seem to be most prominent in the deeper muscles of the body. They are earlier and most vigorous in shoulder girdle, face and arm; they then appear in the trunk and are less striking though still demonstrable in the lower limbs. They are most noticeable, in animals, Dr. Paton is Professor of Pharmacology, Royal College of Surgeons of England, London. when a full paralyzing dose is injected fairly rapidly, and can be reduced by slow injection. With very large doses they appear but rapidly disappear as block ensues. Such observations suggest that the rate of onset of the end-plate depolarization determines the vigor of the ex¬ citation; this conforms with the fact that suc- cinylcholine produces fasciculations more read¬ ily than decamethonium, just as its depolarizing influence is more rapidly exerted. The total duration of fasciculation probably depends on the time taken to pass from the threshold stimulant action to full block. These fasciculations may be associated with the deep muscle ache sometimes evident after the use of stimulant relaxants, and hence are of more than academic significance. It seems clear that they do not represent excitation of individual muscle fibers, for the movements elicited may be quite powerful; further, the electromyographic records obtained represent motor-unit activity, and do not conform with fibrillary responses.3 How may synchronous responses of whole units be elicited by end- plate depolarization? One suggestion made by Masland and Wigton 4 to explain the cen¬ tripetal discharges in a motor nerve of a muscle treated with neostigmine is that an axone re¬ flex is set up. Such retrograde activation of one nerve termination by a depolarized end- plate leads to activity of the whole unit, as well as to centripetal impulses recorded in the nerve trunk. A second possibility is raised by recent work on the muscle spindles. It is known that the junction of the small motor nerve fibers (y fi¬ bers) with the contractile part of the spindle is a cholinergic synapse, and that its activation can lead to a discharge in the afferent nerves.5 Such an afferent discharge is normally the basis of the stretch reflex. Consequently, the admin¬ istration of a depolarizing drug would be ex¬ pected to elicit reflex motor activity. It must