There is evidence that reactive oxygen species (ROS) are involved in the pathophysiology of psychiatric disorders such as schizophrenia. Indirect biochemical alterations of ROS formation have been shown for patients treated with antipsychotics as well as for untreated patients. Only one study measured directly the ROS formation after treatment with antipsychotics by using electron spin resonance spectroscopy. The aim of the present examination was to demonstrate the effects of haloperidol, clozapine and olanzapine in concentrations of 18, 90 and 180 μg/mL on the formation of ROS in the whole blood of rats by using electron spin resonance spectroscopy after incubation for 30 min. To test the protective capacity of vitamin C we incubated the highest concentration of each drug with vitamin C (1 mM). Under all treatment conditions, olanzapine led to a significantly higher formation of ROS compared with control conditions, whereas in the cases of haloperidol and clozapine the two higher concentrations induced a significantly enhanced formation of ROS. Vitamin C reduced the ROS production of all drugs tested and for haloperidol and clozapine the level of significance was reached. Our study demonstrated that antipsychotics induce the formation of ROS in the whole blood of rats, which can be reduced by the application of vitamin C.

Because there are reports on cytotoxic and cytoprotective effects of antipsychotics, the aim of the present study was to evaluate the impacts of different concentrations (1.6-50 microg/mL) of atypical antipsychotics on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and on energy metabolism (ATP level after the incubation with antipsychotics in the concentration of 25 microg/mL). Statistical analysis showed that incubation for 24 h with the antipsychotics quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone led to a significantly enhanced cell survival in both cell lines in the lower concentrations. Higher concentrations exerted in part cytotoxic effects with the exception of quetiapine, but therapeutically relevant concentrations of the drugs were not cytotoxic in our experiments. Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 microg/mL risperidone and 9-hydroxyrisperidone. The other substances produced no effects. Our results show that the antipsychotic substances under investigation exert concentration-dependent effects on cell survival in both cell lines examined.

The oxidative and antioxidative properties of psychostimulants such as methylphenidate and amphetamine are discussed controversially. The aim of the present study was to evaluate the impact of psychostimulants and atomoxetine in different concentrations between 31.25 and 5000 ng/ml on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and the impact of psychostimulants and atomoxetine in different concentrations between 500 and 5000 ng/ml on energy metabolism (adenosine triphosphate [ATP] content) in SH-SY5Y cells. Statistical analysis revealed that incubation for 24 h with amphetamine led to a significantly enhanced cell survival in both cell lines after treatment with various (32.5, 125, 250 and 1250 ng/ml) concentrations. Methylphenidate and atomoxetine induced a significantly enhanced cell survival at lower concentrations in the SH-SY5Y cell line, whereas in the U-937 cell line higher concentrations increased the cell survival. Incubation with the highest concentration of methylphenidate (5000 ng/ml) caused a significant reduction of cell survival in both cell types. Measurement of ATP contents in the neuronal cell line revealed no significant effects of the investigated compounds. Our results show that the examined substances exert concentration-dependent effects on cell survival in both applied cell lines.

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