Curare-like action of poly-methylene bis-quaternary ammonium salts / by W.D.M. Paton and E.J. Zaimis.

  • Paton, William D. M.
Date:
[1948?]
Catalogue details

Licence: In copyright

Credit: Curare-like action of poly-methylene bis-quaternary ammonium salts / by W.D.M. Paton and E.J. Zaimis. Source: Wellcome Collection.

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    {Reprinted from Nature, Vol. 161, page 718, May 8, 1948.) Curare-like Action of Polymethylene bis- Quaternary Ammonium Salts During a test of octamethylene-a^-dis-trimethyl- ammonium chloride for the power of liberating histamine, it was observed to be remarkably effective as a cause of neuromuscular block. Accordingly, a series of straight-chain aliphatic ao-6is-trimethyl- ammonium iodides have been sjmthesized from diamines by treatment in methyl alcoholic solution with methyl iodide and sodium hydroxide, and using the insolubility of these compounds in acetone, and the solubility of sodium iodide in this solvent for their isolation. All the compounds synthesized were tested for potency, and the octamethylene derivative (C8) was the subject of more detailed pharmacological study. In the rabbit head-drop test for curare-like activity, potency increased from the ethylene derivative to the octamethylene derivative, and the decamethylene derivative (C10) was more potent still, 0-11 mgm./kgm. of the iodide being required to produce head-drop, compared with 0-25 mgm./kgm. of d-tubocurarine chloride. The potency in relation to d-tubocurarine chloride varied, however, with the test object ;• thus, the approximate ratio of an effective dose of the C8 derivative to an equipotent dose of d-tubocurarine chloride was, on the cat’s tibialis, £ ; on rabbit’s head-drop, 3 ; on frog nerve-sartorius preparation, 3 ; on rat’s diaphragm preparation, 50-100. In the cat’s tibialis preparation1, the C8 derivative prevented the response of the muscle to stimulation of its motor nerve and to close arterial injection of acetylcholine, but not its response to direct stimulation. The con¬ duction of impulses in nerve trunks was not affected by it. While large doses of the C8 derivative caused rapid neuromuscular block, moderate doses injected intra¬ venously in the cat initially increased the response of tibialis to single maximal shocks applied to the motor nerve, and this response was followed by a small prolongation of the contraction, together with a widespread fibrillation of the musculature for 20-30 sec. not unlike that resulting from the injection of anticholinesterases. Intra-arterial injection of the C8 derivative in a dose of 20 ggm. into the cat’s l