Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells

A variety of dopaminergic ligands were evaluated for their ability to alter glucose transport in PC12 cells. Certain antipsychotic drugs which targeted D2 dopamine receptors, such as pimozide, fluphenazine and chlorpromazine, inhibited glucose uptake (with IC50's in the range of 2-40 microM). By contrast, haloperidol and sulpiride (also D2 antagonists) showed marginal activity. The atypical antipsychotic drug, clozapine (a D4 antagonist), also effectively inhibited glucose transport by the cells. Ligands specific for D1 receptors did not interfere with glucose uptake. Time course studies revealed that a short incubation with the drugs (1-5 min) was sufficient to block glucose transport. These findings may have implications for the adverse effects of these drugs and for the interpretation of imaging studies of brain glucose metabolism in patients on antipsychotic medications.