The perturbation of lipid bilayers by general anesthetics: a quantitative test of the disordered lipid hypothesis
Pang, K.Y.; Braswell, L.M.; Chang, L.; Sommer, T.J.; Miller, K.W.
Molecular Pharmacology 18(1): 84-90
1980
ISSN/ISBN: 0026-895X PMID: 7412765 Document Number: 160650
The ability of a wide range of general anesthetics to perturb the order reported from spin-labeled phospholipid:cholesterol (2:1) bilayers was examined. The change in order induced by increasing concentrations of the following were examined: ethanol, butanol, trichloroethanol, .alpha.- 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, phenytoin 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. 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. The disordered lipid hypothesis is fairly successful at correlating the anesthetic potency data over a dose range of 4 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.