A spin label study of the perturbation effect of tertiary amine anesthetics on brain lipid liposomes and synaptosomes

The membrane disordering efficiency of four local anesthetics, including lidocaine, tetracaine, dibucaine and heptacaine (piperidinoethyl ester of 2-heptyloxyphenylcarbamic acid) has been studied by spin-labeling methods. The disordering efficiency of the drugs in rat total brain lipid liposomes was quantitated with the initial slope value of the order parameter versus drug concentration curve, the so-called change-in-order parameter value. Using the positional isomers of m-doxyl stearic acids (m = 5, 12 and 16), it has been demonstrated that the tested drugs reveal quite different disordering efficiency. There is a clear tendency of increasing disordering efficiency towards the methyl terminal of the lipid acyl chains. By a comparison of order parameter versus drug concentration and temperature at three depths of rat brain total lipid liposomes and synaptosomes, it is shown that the ‘fluidizing effect’ of local anesthetics does not correspond to fluidization of membrane by temperature and that tetracaine and dibucaine do not have equal disordering efficiency as judged by their solubility in the membrane. The disordering efficiency of these drugs on the hydrocarbone core of a membrane qualitatively corresponds to their anesthetic potency. Similar results were obtained in liposomes and synaptosomes. It is assumed that there is a similar incorporation of the local anesthetics in the liposomes and in the lipid part of synaptosomes.