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Interaction of halothane with lipid bilayers.

Sidney A. Simon,T. J. McIntosh,PB Bennett,B. Shrivastav

Published 1979 in Molecular Pharmacology

ABSTRACT

The bilayer-saline partition coefficient of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) was directly measured as a function of temperature in phospholipids of various hydrocarbon chain lengths and degrees of saturation, both with and without cholesterol. The major conclusions of this research can be summarized as follows: 1) The bilayer-saline partition coefficient as a function of temperature is similar for the lipids dilaurylphosphatidylcholine, dioleoylphosphatidylcholine and egg phosphatidylcholine over a temperature range from 10 to 60°, where each lipid is in the liquid-crystalline state. Over this range the partition coefficient versus temperature curve exhibits a change from positive to negative slope for all three lipids. 2) The bilayer-saline partition coefficient increased with increasing temperature by a factor of 4 at the phase transition (40°) of dipalmitoylphosphatidylcholine. At this temperature, the partition coefficients of all four lipids mentioned were similar. 3) The addition of cholesterol to egg phosphatidylcholine reduces the partition coefficient by a factor of 2 at a 2:l mole ratio and 2.7 at a 1:l mole ratio at 25°. In these bilayers the partition coefficient was independent of temperature. 4) From (3) and other data we suggest that the reduced partial pressure necessary to produce anesthesia at lower temperatures for halothane is not due to an increase in the bilayer-saline partition coefficient.

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