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. 1981 Sep;74(1):161–170. doi: 10.1111/j.1476-5381.1981.tb09969.x

Additive and non-additive effects of mixtures of short-acting intravenous anaesthetic agents and their significance for theories of anaesthesia

CD Richards, Ann E White
PMCID: PMC2071874  PMID: 6268237

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Archer E. R., Richards C. D., White A. E. Non-additive anaesthetic effects of alphaxalone and methohexitone [proceedings]. Br J Pharmacol. 1977 Mar;59(3):508P–508P. [PMC free article] [PubMed] [Google Scholar]
  2. Card B., McCulloch R. J., Pratt D. A. Tissue distribution of CT 1341 in the rat; an autoradiographic study. Postgrad Med J. 1972 Jun;48(Suppl):34–37. [PubMed] [Google Scholar]
  3. Clarke R. F., Daniels S., Harrison C. B., Jordan M. J., Paton W. D., Smith E. B., Smith R. A. Potency of mixtures of general anaesthetic agents. Br J Anaesth. 1978 Oct;50(10):979–983. doi: 10.1093/bja/50.10.979. [DOI] [PubMed] [Google Scholar]
  4. Cullen S. C., Eger E. I., 2nd, Cullen B. F., Gregory P. Observations on the anesthetic effect of the combination of xenon and halothane. Anesthesiology. 1969 Oct;31(4):305–309. doi: 10.1097/00000542-196910000-00003. [DOI] [PubMed] [Google Scholar]
  5. DiFazio C. A., Brown R. E., Ball C. G., Heckel C. G., Kennedy S. S. Additive effects of anesthetics and theories of anesthesia. Anesthesiology. 1972 Jan;36(1):57–63. doi: 10.1097/00000542-197201000-00010. [DOI] [PubMed] [Google Scholar]
  6. Miller K. W., Paton W. D., Smith E. B., Smith R. A. Physicochemical approaches to the mode of action of general anesthetics. Anesthesiology. 1972 Apr;36(4):339–351. doi: 10.1097/00000542-197204000-00008. [DOI] [PubMed] [Google Scholar]
  7. Miller K. W., Paton W. D., Smith R. A., Smith E. B. The pressure reversal of general anesthesia and the critical volume hypothesis. Mol Pharmacol. 1973 Mar;9(2):131–143. [PubMed] [Google Scholar]
  8. Miller R. D., Wahrenbrock E. A., Schroeder C. F., Knipstein T. W., Eger E. I., 2nd, Buechel D. R. Ethylene--halothane anesthesia: addition or synergism? Anesthesiology. 1969 Oct;31(4):301–304. [PubMed] [Google Scholar]
  9. Richards C. D., Hesketh T. R. Implications for theories of anaesthesia of antagonism between anaesthetic and non-anaesthetic steroids. Nature. 1975 Jul 17;256(5514):179–182. doi: 10.1038/256179a0. [DOI] [PubMed] [Google Scholar]
  10. Richards C. D., Martin K., Gregory S., Keightley C. A., Hesketh T. R., Smith G. A., Warren G. B., Metcalfe J. C. Degenerate perturbations of protein structure as the mechanism of anaesthetic action. Nature. 1978 Dec 21;276(5690):775–779. doi: 10.1038/276775a0. [DOI] [PubMed] [Google Scholar]
  11. Richards C. D. On the mechanism of barbiturate anaesthesia. J Physiol. 1972 Dec;227(3):749–767. doi: 10.1113/jphysiol.1972.sp010057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Richards C. D., Russell W. J., Smaje J. C. The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex. J Physiol. 1975 Jun;248(1):121–142. doi: 10.1113/jphysiol.1975.sp010965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Richards C. D., Tegg W. J. A superfusion chamber suitable for maintaining mammalian brain tissue slices for electrical recording [proceedings]. Br J Pharmacol. 1977 Mar;59(3):526P–526P. [PMC free article] [PubMed] [Google Scholar]
  14. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  15. Trudell J. R. A unitary theory of anesthesia based on lateral phase separations in nerve membranes. Anesthesiology. 1977 Jan;46(1):5–10. doi: 10.1097/00000542-197701000-00003. [DOI] [PubMed] [Google Scholar]
  16. WELLES J. S., McMAHON R. E., DORAN W. J. The metabolism and excretion of methohexital in the rat and dog. J Pharmacol Exp Ther. 1963 Feb;139:166–171. [PubMed] [Google Scholar]

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