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Molecular Pharmacology, Vol 9, 131-143, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

The Pressure Reversal of General Anesthesia and the Critical Volume Hypothesis

K. W. MILLER 1, W. D. M. PATON 1, R. A. SMITH 1, and E. B. SMITH 1

1 Department of Pharmacology and Physical Chemistry Laboratory, Oxford University, Oxford, England

The anesthetic potencies (ED50) of four gaseous anesthetics and five liquid anesthetics were first determined in newts, using the abolition of righting reflex measured by the rolling response at 20°. The following results were obtained: N2O, 0.69 atm; N2, 21.5 atm; SF6, 1.82 atm; CF4, 11.0 atm; CHCl3 0.89 mM; butanol, 16.7 mM; pentobarbitone sodium, 0.85 mM; halothane, 0.39 mM; ether, 25 mM. The ability of elevated pressures to antagonize the effect of these anesthetics was then studied. For the liquid anesthetics, a graded response to pressure was observed and the reversibility of the antagonistic effect was demonstrated. Dose-response curves were obtained for the interaction of pressure with the gaseous anesthetics, and, from these, ED50 values at various pressures have been interpolated. The data are used to compare the Meyer-Overton and the critical volume hypotheses; the latter not only is consistent with the data but also provides explanations for the antagonistic phenomenon and the lack of anesthetic effect for helium, neon, and hydrogen. The critical volume hypothesis is developed for three solvent model systems, from which estimates of the compressibility of the site of action are made.

Submitted on September 5, 1972




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