A comparative study of the plasma membrane permeabilization and fluidization induced by antipsychotic drugs in the rat brain Short Title: Effects of antipsychotic drugs on plasma membrane Manuscript Categories: Brief Reports

We compared the potency of the interaction of three antipsychotic drugs, i.e., chlorpromazine (CPZ), haloperidol (HAL) and sulpiride (SUL), with the plasma membrane in the rat brain. CPZ loading (≥ 100 μM) dose-dependently increased both membrane permeability (assessed as [F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of HAL (1 mM) was required to observe these effects. However, SUL failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to interact with the membrane: CPZ > HAL > SUL. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side effects such as parkinsonism and tardive dyskinesia.