The margins of safety for neuromuscular transmission in the gastrocnemius and diaphragm muscle of the cat and the rabbit have been determined indirectly by a modified dose-ratio method. The dose-ratio is the ratio of the doses of agonist required to produce a given degree of the drug action (50% decrease of indirectly elicited mechanical response) in the presence and in the absence of a subclinically effective dose of antagonist. In the present study the assumption was made that following the application of agonist, the fraction of muscle fibres unresponsive to indirect stimulation reflected the degree of sustained depolarization of the end-plate region. Suxamethonium was used as agonist, tubocurarine was used as antagonist. With stimulation once every 10 sec, the dose-ratios were 1.9±0.4 (mean±SD) and 2.0±0.3 in the cat gastrocnemius and the diaphragm muscle respectively. In the rabbit, the corresponding dose-ratios were 1.3±0.1 and 1.3±0.2. It is suggested that there may be a species-related difference in the safety margin for gastrocnemius muscle. In both species, there was no significant difference between gastrocnemius and diaphragm.
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