Abstract

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, α- and β-chloralose, urethane, pentobarbital, thiopental, ketamine, and phenytoin. All except the latter and β-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.