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Molecular Pharmacology, Vol 18, 84-90, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

The Perturbation of Lipid Bilayers by General Anesthetics: A Quantitative Test of the Disordered Lipid Hypothesis

KAM-YEE Y. PANG 1, LEON M. BRASWELL 1, LARRY CHANG 1, TOBY J. SOMMER 1, and KEITH W. MILLER 1

1 Departments of Anaesthesia and Pharmacology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114

The ability of a wide range of general anesthetics to perturb the order reported from spin-labeled phospholipid:cholesterol (2:1) bilayers has been examined. The change in order induced by increasing concentrations of the following were examined: ethanol, butanol, trichloroethanol, agr- and beta-chloralose, urethane, pentobarbital, thiopental, ketamine, and phenytoin. All except the latter and beta-chloralose caused marked decreases in order. The bilayer/buffer partition coefficients of phenobarbital, phenytoìn, and urethane were measured. The change-in-order parameter as a function of total anesthetic concentration varied widely but when the agents were compared at constant concentration in the bilayer all the anesthetics examined gave very similar values. Phenobarbital was somewhat more effective at disordering than the other barbiturates. Phenytoin's weak disordering ability was probably due to solubility limitations rather than an inability to disorder. When the general anesthetic and nerve-blocking potency of these agents were compared to their membrane disordering ability, fair correlations were obtained, but the barbiturates tended to deviate and this deserves further attention. Furthermore the change-in-order parameter at general anesthetic concentrations is only 0.6% which is small compared to the variation to be expected in the physiological temperature range. Thus although the disordered lipid hypothesis is fairly successful at correlating the anesthetic potency data over a dose range of four orders of magnitude, some problems remain. How far these can be overcome by developing more realistic models within the framework of the hypothesis remains to be seen.

Note:
ACKNOWLEDGMENT We wish to thank Dr. J. Gergeley, Boston Biomedical Research Institute, for use of election spin resonance equipment.

Submitted on June 22, 1979
Accepted on January 21, 1980




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M. Pickholz, L. Saiz, and M. L. Klein
Concentration Effects of Volatile Anesthetics on the Properties of Model Membranes: A Coarse-Grain Approach
Biophys. J., March 1, 2005; 88(3): 1524 - 1534.
[Abstract] [Full Text] [PDF]


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