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Characteristics of nondepolarizing neuromuscular block: (I) post-junctional block by alpha-bungarotoxin

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Summary

The characteristics of neuromuscular block produced by alpha-bungarotoxin, a post-junctionally active polypeptide toxin purified from snake venoms, have been studiedin vivo in 12 anaesthetized cats, using the sciatic nerve-tibialis anterior muscle preparation. The onset of the neuromuscular block was slow and without fasciculation. The block was persistently progressive. The time course of the block depended on the dosage. In general, 0.1 mg/kg of alpha-BuTX appeared to approximate the threshold dosage while 0.2 mg/kg completely eliminated the twitch response in 2-5 hours. No recovery was observed in 8-30 hours. Larger doses accelerated the progression of the block. During the block, tetanic contractions and train-of-four twitches did not fade. The post-tetanic twitches were markedly facilitated. The block was antagonized by edrophonium, neostigmine, pyridostigmine, and succinylcholine, but the antagonism was less effective and shorter-lasting than that observed on curare-block, and the block always resumed the projected progression. Attempts were made to explain the observed difference between alpha-BuTX-and dTc-induced neuromuscular blocks by the practically permanent nature of block and the purely post-junctional site of action of alpha-BuTX. It was concluded that a pure post-junctional block is not characterized by fade, which rather might be a pre-junctional effect of some nondepolarizing neuromuscular blocking agents like d-tubocurarine.

Résumé

La d-Tubocurarine agit à la fois à ľextrémité du nerf moteur et à la plaque motrice de la fibre musculaire (actions pré et post-synaptique). Le bloc musculaire qu’elle produit se caractérise par une absence de fasciculations, un affaiblissement de la “série de quatre” (train of four), une facilitation post-tétanique et, enfin, ce bloc est renversé par les anti-cholinesterases.

Dans le but de mettre en relation ces différentes caractéristiques avec un mécanisme ďaction pré et post-synaptique, nous avons fait ľétude ďun agent dont ľaction se limite à la région post-synaptique.

Ľalpha-bungarotoxine, une polypeptide extraite de venins de serpents, répond à ce critère en agissant uniquement à la région post-synaptique. Aussi, nous avons précisé les caractéristiques du bloc qu’elle produit in vivo, au moyen de préparation sciatique-tibial antérieur, ceci chez 12 chats anesthésiés.

Le bloc s’installait lentement sans que ľon observe de fasciculations et augmentait ďintensité avec le temps, en fonction de la dose. Une dose de 0.1 mg/kg était la dose-seuil nécessaire pour obtenir unblocage au moins partiel, alors qu’une dose de 0.2 mg/kg éliminait complètement la réponse au “twitch” au bout de deux à cinq heures. Ľabsence de réponse persistait de 8 à 30 heures. Les doses plus importantes accéleraient la vitesse de ľétablissement du blocage.

Durant la période du bloc, on n’a pas observé ďaffaiblissement des contractions tétaniques et de la “série de quatre.” La facilitation post-tétanique était augmentée de façon importante.

Ľedrophonium, la neostigmine, la pyridostigmine et la succinylcholine renversent ce bloc mais de façon moins complète et de façon plus courte que lorsqu’il s’agit ďun bloc au curare; le bloc réapparaît toujours pour continuer à progresser.

Nous avons tenté ďexpliquer les différences observées par la nature presque permanente du bloc produit et par le fait que ľaction est exclusivement postsynaptique. On en conclut qu’un bloc limité à la région post-synaptique ne se caractérise pas par un affaiblissement de la série de quatre, contrairement au bloc de la d-tubocurarine.

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Correspondence to Chingmuh Lee or Dennis Chen or Ronald L. Katz.

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Lee, C., Chen, D. & Katz, R.L. Characteristics of nondepolarizing neuromuscular block: (I) post-junctional block by alpha-bungarotoxin. Canad. Anaesth. Soc. J. 24, 212–219 (1977). https://doi.org/10.1007/BF03006234

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Keywords

  • Neostigmine
  • Neuromuscular Block
  • Snake Venom
  • Tibialis Anterior Muscle
  • Pyridostigmine