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Molecular Pharmacology, Vol 12, 127-135, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Site and Mechanism of Anesthetic Action

I. Effect of Anesthetics and Pressure on Fluidity of Spin-Labeled Lipid Vesicles

J. M. BOGGS 1, T. YOONG 1, and J. C. HSIA 1

1 Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

The lipid expansion hypothesis of anesthesia has been re-examined. We have measured the effect of anesthetics and pressure on the order parameter of phosphatidylcholine-cholesterol bilayer vesicles labeled with fatty acid spin labels. Concentrations of halothane, chloroform, diethyl ether, butanol, and benzyl alcohol which produce general anesthesia have no significant effect on the order of the bilayer structure, while 100 atm of helium have a constant small ordering effect with or without anesthetics. The lack of correlation between anesthetic and pressure effects on lipid model membranes fails to support the lipid fluidization hypothesis of anesthesia or to account for pressure reversal of general and local anesthesia.

Submitted on December 16, 1974






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