The mechanisms of motor end-plate depolarization due to a cholinesterase-inhibiting drug / by W.W. Douglas and W.D.M. Paton.

  • Douglas, W. W.
Date:
[1954?]
Catalogue details

Licence: In copyright

Credit: The mechanisms of motor end-plate depolarization due to a cholinesterase-inhibiting drug / by W.W. Douglas and W.D.M. Paton. Source: Wellcome Collection.

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    of the depolarization is considerably increased with these larger doses, and it may still be detectable 1 hr after a dose of 2 mg/kg. There was always a distinct latency in this depolarizing action of large doses, and although it was briefer than with small doses, it was never less than 26 sec. This is at least twice as long as that preceding the action of acetylcholine or of decamethonium injected by the same route. These two substances depolarize the end-plates often within 6 sec and always within 12 sec of making the intravenous injection. (0 Fig. 5. Cat, chloralose, tibialis prepared for close arterial injection. Supramaximal stimulus to sciatic nerve every 10 sec, intermitted at close arterial injections: (a) 0-1 mg TEPP close arterially; (b) 0-5 mg TEPP close arterially; (c) 2-5/u.g acetylcholine given twice close arterially, followed by TEPP 1-0 mg. The absence of a direct muscle stimulating effect of TEPP Despite the fact that both TEPP (in large doses) and directly acting com- pounds can produce closely similar end-plate depolarizations, there were two important differences between TEPP and these other substances: first, the effects of small doses of TEPP were quite unlike those of small doses of acetyl¬ choline or decamethonium; secondly, even with the biggest doses of TEPP there was a considerable latency in its action. It was therefore important to test more directly whether TEPP had an immediate stimulant action, by trying whether it could elicit an immediate contraction of the tibialis muscle when injected close arterially. The results of two experiments are shown in Fig. 5. Doses of TEPP from 0*1 to 1 mg, injected close arterially, never elicited a twitch, although the muscle responded vigorously to as little as 2*5 /xg acetylcholine. Soon after