Clinical potentialities of certain bisquaternary salts causing neuromuscular and ganglionic block / [W.D.M. Paton, E.J. Zaimis].

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

Licence: In copyright

Credit: Clinical potentialities of certain bisquaternary salts causing neuromuscular and ganglionic block / [W.D.M. Paton, E.J. Zaimis]. Source: Wellcome Collection.

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    the animal for ten minutes, and weakness for an hour. Similar observations have been made in unansesthetized and anaesthetized cats, and (to a less extent) in the rabbit. The ratio of the dose which just suspends respiration in half the animals to that which produces definite weakness for at least 10 min. has been estimated, as an index of the relative activity on respiratory and other muscles. In the monkey, the ratio is 2-6 for the C 10 compound, and T5 for d-tubocurarine ; in the cat, the ratios are respectively 2*2 and 1-25. In the rabbit we have not been able to demonstrate any significant difference by this method, the ratio in both cases being close to unity. It is also noteworthy that the duration in the monkey of a paralysis due to the C 10 com¬ pound is usually two to three times longer than that of one of equal initial intensity due to d - tub o curarine chloride. Eserine and prostigmine do not antagonize the C 10 compound ; but a lower member of the series, C 5, has proved to be a useful antagonist. In all three species, an injection of 0*5-5 mgm./kgm. of C 5 cuts short a moderate or shallow paralysis, accelerates recovery from a deep curarization, and restores to normal a respiration that is becoming inade¬ quate, where these conditions are due to the C 10 compound. The G 10 compound must be compared with d-tubocurarine chloride in two other respects : (a) the latter is active in paralysing autonomic ganglia, and may thereby cause a small fall in blood pressure ; the former exhibits some activity of this kind, but requires a dose five to ten times as great to produce the same effect; (b) the latter is known to liberate histamine8, and such liberation might cause undesirable side-effects ; the former can also be shown to produce an effect on the blood pressure characteristic of histamine liberation® ; but it requires a dose at least four times larger. We have confirmed Barlow and Ing’s7 finding that this series of com¬ pounds possesses a weak anti-esterase activity ; but this activity does not appear to produce any side actions, except possibly the fine fasciculations in the rabbit mentioned above. Chronic toxicity tests have shown that rabbits and cats can receive curarizing doses of the C 10 compound daily for six weeks without change in type or degree of the paralysis, or deterioration in the health of the animal.