Effects of quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone on the survival of human neuronal and immune cells in vitro

Abstract

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.

Neuroprotection of paliperidone on SH-SY5Y cells against β-amyloid peptide25-35, N-methyl-4-phenylpyridinium ion, and hydrogen peroxide-induced cell death

“…Overall, paliperidone had the best at concentrations of 10 and 50 μM, even though it retained a mild cytotoxicity when the high dosage was used. This finding is partly consistent with a recent report from Schmidt et al (2010) in which they also showed that incubation for 24 h with risperidone and paliperidone (9-hydroxy risperidone) led to a significantly enhanced cell survival in SH-SY5Y cells in the lower concentrations. Higher concentrations exerted in part cytotoxic effects, with the exception of quetiapine (Schmidt et al 2010).…”

“…This finding is partly consistent with a recent report from Schmidt et al (2010) in which they also showed that incubation for 24 h with risperidone and paliperidone (9-hydroxy risperidone) led to a significantly enhanced cell survival in SH-SY5Y cells in the lower concentrations. Higher concentrations exerted in part cytotoxic effects, with the exception of quetiapine (Schmidt et al 2010). Measurement of ATP contents in SH-SY5Y cell line showed significantly increased levels after a 24-h treatment with 25 μM risperidone and paliperidone (9-hydroxy risperidone), which may represent a high effectiveness in excitement of ATP-dependent cellular activities by these two drugs.…”

“…However, paliperidone has not been determined for its neuroprotective effect on neuronal cell via cell base assay. A recent study showed that paliperidone enhanced the cell survival of SH-SY5Y and U937 cells (Schmidt et al 2010), two cell lines separately representing neural and immune cell types which are usually involved in the pathogenesis of schizophrenia. In an ex vivo study through a proteomic approach, paliperidone was proposed to have a model of action similar to lithium and valproic acid due to stimulated similar protein expression profile in treating the synaptoneurosomalenriched prefrontal cortex.…”

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

“…The drug concentrations tested here comprised of haloperidol (20 μM=7.55 μg/ mL; 30 μM=11.27 μg/mL and 40 μM=15 μg/mL) and risperidone (20 μM=8.20 μg/mL; 30 μM=12.31 μg/mL and 40 μM=16.4 μg/mL). These concentrations were chosen in line with the investigation performed by Schmidt et al (2010), whereby the authors evaluated the effect of some antipsychotics, including risperidone, on the survival of human neuronal and immune cells. In the SH-SY5Y and U-937 cells, these concentrations were not cytotoxic.…”

The Pharmacological Role and Clinical Applications of Antipsychotics’ Active Metabolites: Paliperidone versus Risperidone

“…Both cell lines are considered to be involved in the pathogenesis of schizophrenia. In this model, low concentrations of risperidone (1.6-12.5 μg/mL) increase cell survival, while paliperidone significantly improves survival of SH-SY5Y cells and U-937 cells at a concentration of 1.6 μg/mL [128].…”