Differential Cytotoxicity of Drugs Acting in the Central Nervous System in SH-SY5Y Cells: Toxic Mechanisms of Fluoxetine and Haloperidol

초록

Recently, several evidences suggested that some drugs acting in the central nervous system (CNS) may have toxic effect on neuronal cells. Here, we evaluated the effects of various CNS drugs with differential pharmacologic mechanisms on cell viability in SH-SY5Y cells. Fluoxetine (antidepressants; selective serotonin reuptake inhibitor) and haloperidol (antipsychotics; D2 receptor antagonist) showed cytotoxicity at clinically reasonable concentrations. However, other drugs (gabapentin, risperidone, propofol, amitriptyline, and ketamine) did not induce cell death. When cells treated with fluoxetine or haloperidol and MPP+ (1-methyl-4-phenylpyridinium), an additive cytotoxic effect was observed. Instead, propofol inhibited the MPP+-induced cell death. Fluoxetine and haloperidol activated JNK and caspase-3, but not p38-MAPK. Neither fluoxetine nor haloperidol increased superoxide or nitrotyrosine production. Since the fluoxetine-, or haloperidol-induced catecholaminergic cell death may be associated with dopaminergic neurodegeneration, further in vivo study should be conducted to elucidate the clinical meanings of current study