The methonium compounds / by W.D.M. Paton and Eleanor J. Zaimis.

  • William Paton
Date:
[1952?]
Catalogue details

Licence: In copyright

Credit: The methonium compounds / by W.D.M. Paton and Eleanor J. Zaimis. Source: Wellcome Collection.

    8/36 (page 226)
    far the most thoroughly studied. (It must be remembered, however, that there are indications (114, 131) that a small part of its activity is due to properties other than that of competition with acetylcholine, and the ideal representative has probably yet to be found.) 1. ) The action of d-tubocurarine at the neuromuscular junction is simply that of pure competition; this results in a single uniform picture of neuromuscular paralysis. The course of the paralysis is similar in all species and with all muscles and is never preceded by potentiation of the twitch nor accompanied by con¬ tracture. The scattered exceptions to this statement [evidence of contracture of the dog’s denervated gastrocnemius (114) and of denervated rats triceps (95)], do not significantly alter this generalization. 2. ) The muscle partially paralysed by d-tubocurarine cannot maintain a tetanus at its initial strength. Although, in a lightly curarized muscle, the ten¬ sion may initially be comparable to that of a normal muscle, it falls rapidly thereafter to a much lower level. As the dose of curare increases and as the fre¬ quency of tetanisation increases, the ratio of the subsequent contraction height to the initial tension becomes smaller and smaller, and finally becomes zero even though there may still be a fairly vigorous initial twitch. The cause of this flagging tetanic contraction is not established, although no doubt a waning of the acetylcholine output per nerve volley as the tetanus proceeds is an important factor. It constitutes, however, an important aspect of the action of curare-like substances and contributes, for instance, to the greater depression of tetanic activities (such as respiration) than of muscle twitches (141). 3. ) Muscles vary appreciably in their sensitivity to d-tubocurarine. It has long been known that ocular, cranial and bulbar muscles and those of the hand are outstandingly sensitive. In the cat, likewise, soleus is much more sensitive than tibialis, and the respiratory muscles resemble soleus (141). 4. ) Block by curare is antagonized by a wide range of drugs and procedures, including anticholinesterases, adrenaline, asphyxia, potassium, previous teta¬ nisation, acetylcholine and other depolarizing drugs, phenol, and the ra-OH phenylalkylammonium compounds (for references, see 94, 126, 128). 5. ) Block by curare is intensified by substances which raise the endplate threshold to acetylcholine, such as ether anaesthesia, atropine (in large doses) and other substances producing neuromuscular block in the same way as d- tubocurarine (137, 141, 143). 6. ) The presence of curare diminishes the effect of depolarizing drugs, if administered beforehand, and reverses it if given subsequently (38, 112, 137). 7. ) If cathodal current is passed at the endplate region of a partially curarized muscle, the intensity of the block is instantly diminished and normal transmis¬ sion may be restored. Anodal current, on the other hand, intensifies the paralysis (c/. 31a). 3. Characteristics of neuromuscular block due to endplate depolarization We have taken decamethonium in its action on cat, avian and frog muscle as the best representative of drugs producing depolarization block, and in de-