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ADDITIVE AND NON‐ADDITIVE EFFECTS OF MIXTURES OF SHORT‐ACTING INTRAVENOUS ANAESTHETIC AGENTS AND THEIR SIGNIFICANCE FOR THEORIES OF ANAESTHESIA

1 The potency of a series of short‐acting anaesthetics was established by measuring the duration of the loss of righting reflex following a single bolus injection into the tail vein of male Wistar rats. The agents were, in order of potency, etomidate, alphaxalone, methohexitone, alphadalone acetate and propanidid 2 The potency of binary mixtures of these agents was also assessed to see whether the anaesthetic effects of different agents were additive as classical theories of anaesthesia suggest. Mixtures of alphaxalone and alphadalone acetate, alphaxalone and propanidid and methohexitone and propanidid all showed simple additive effects. Mixtures of alphaxalone and etomidate and of alphaxalone and methohexitone showed a greater potency than would be expected if their effects were simply additive. Mixtures of etomidate and methohexitone were not examined 3 Mixtures of alphaxalone and either methohexitone or pentobarbitone produced a greater depression of synaptic transmission in in vitro preparations of guinea‐pig olfactory cortex than would have been expected from the sum of the activities of the individual anaesthetics. Other combinations of anaesthetics did not show similar effects although the interaction between alphaxalone and etomidate was not examined 4 Neither alphaxalone nor pentobarbitone affected the membrane: buffer partition coefficient of the other for a model membrane system 5 These results are interpreted as evidence against the classical unitary hypotheses of anaesthetic action based on correlations of anaesthetic potency with lipid solubility and as supporting the view that different anaesthetics act on different structures in the neuronal membranes to produce anaesthesia.