Inhibition by phenothiazine antipsychotic drugs of calcium-dependent phosphorylation of cerebral cortex proteins regulated by phospholipid or calmodulin

Phospholipid-sensitive and calmodulin-sensitive Ca²⁺-dependent phosphorylation of a number of endogenous proteins in the soluble and particulate fractions of the rat cerebral cortex was inhibited by phenothiazine antipsychotic drugs. The mean IC₅₀ values (concentrations causing 50% inhibition of phosphorylation) for trifluoperazine, chlorpromazine and fluphenazine were 16, 24 and 27 μM, respectively. Dibucaine, a local anesthetic drug, was much less effective. It appears that these neuroleptic agents may be useful tools for the study of Ca²⁺-dependent protein phosphorylating systems regulated by either phospholipid or calmodulin in the brain.