Cytotoxicity of conventional and atypical antipsychotic drugs in relation to glucose metabolism.
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.
Dwyer
Donard S
DS
Departments of Psychiatry and Pharmacology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. ddwyer@lsuhsc.edu
Lu
Xiao-Hong
XH
Bradley
Ronald J
RJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3; D007150:Immunohistochemistry; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000187:drug effects; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D051381:Rats
D014150:Antipsychotic Agents; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495690:Slc2a3 protein, rat; D005947:Glucose