AbstractThe purpose of this study was to determine if the depression of calcium‐dependent glutamate release from synaptosomes derived from the rat amygdala is specific to neuroleptics. To this end the effects of nine nonneuroleptic agents and nine previously untested neuroleptic agents (or isomers) on nondependent and calcium‐dependent glutamate release were determined by gas‐chromatographic and radioisotopic methods. All of the neuroleptics except reserpine depressed calcium‐dependent release at 10−7M with only a weak, inconsistent reduction of nonspecific release. None of the nonneuroleptic agents at concentrations of 10−6M 10−5M produced depression of calcium‐dependent release withoutalsostrongly depressing nonspecific release. Reserpine was without effect on release at concentrations as high as 10−7M. Also shown was that the representive neuroleptics Haloperidol, chlorpromazine, and clozapine depressed the calcium‐dependent release of glutamine‐derived glutamate to a greater extent over glucose derived glutamate. These data suggest that the specific depression ofstimulus‐coupledglutamate release is not a characteristic of noneuroleptic compounds, but is highly associated with neuroleptics of the phenothiazine o