Quantitative Examination of the Interaction of Competitive Neuromuscular Blocking Agents on the Indirectly Elicited Muscle Twitch

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Abstract
Gallamine, metocurine, pancuronium and d-tubocurarine were compared when given alone and in combination with isolated guinea pig nerve-lumbrical preparations stimulated via the nerve. The experimental design was set up to control the effects of variation among preparations, order of administration and time of administration (i.e., fresh vs. older preparation). The result was an assay able to measure potentiation with a coefficient of variation of 3%. A format for a graphic presentation to summarize such results is presented and discussed. Two combinations, gallamine plus d-tubocurarine and gallamine plus pancuronium, showed no sign of an interaction beyond that to be expected from a simple competitive interaction. Two others, metocurine plus pancuronium and gallamine plus metocurine, showed about a 2-fold greater potency when combined than would have been expected. The last 2 sets, pancuronium plus d-tubocurarine and metocurine plus d-tubocurarine, showed a slight degree of potentiation. The deviation from simple additivity seen in vivo evidently persists when examined in a system free from artifacts associated with uptake and distribution in the whole organism.