The goal of these studies was to analyze the cytotoxicity of both the conventional and atypical antipsychotic drugs in relation to their effects on glucose metabolism. The drugs were evaluated for their effects on the viability of PC12 cells, which are an established model of neuronal cells in culture. In general, the conventional drugs, such as chlorpromazine, fluphenazine and pimozide, were more toxic than the atypical drugs, including clozapine, quetiapine and risperidone. Olanzapine was unique in that it stimulated cell proliferation in this system. There was a good correlation between the cytotoxicity of a drug and its ability to block glucose transport, although there were some exceptions to this trend. Conventional antipsychotics also affected the expression of glucose transporter proteins in whole cell extracts and at the cell surface. Overall, the data support the notion that many of the antipsychotic drugs associated with the development of movement disorders in patients are cytotoxic for cultured cells.
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