“
“Antipsychotic drugs (APDs) were widely used in treating schizophrenia. Some APDs were reported to have neuroprotective effects against neurotoxicants in the cell level.

Thus, one typical APD (haloperidol) and three atypical

APDs (paliperidone, olanzapine, and risperidone) were tested whether they provide neuroprotection against stressor-induced cell death of SH-SY5Y.

Hydrogen peroxide, N-methyl-4-phenylpyridinium ion, and beta-amyloid peptide were used to treat cells with or without preconditioning by APDs; cell survival and indicators of oxidative stress were measured, respectively.

Paliperidone has the lowest baseline cytotoxicity compared with other Selleck INCB018424 APDs at 24 h; in addition, the paliperidone group showed a better survival than the other APD groups (P < 0.05). In stressor challenging, with a fixed PD332991 concentration of stressors, olanzapine provided the best neuroprotection at 100 mu M against A beta(25-35) and MPP+ (P < 0.05).

In contrast, paliperidone works finely at low concentrations (10 and 50 mu M) against A beta(25-35) and MPP+ and solely protected SH-SY5Y from hydrogen peroxide. At 100 mu M, paliperidone completely diminished cell reduction induced by different stressors, regardless of their dosages. Paliperidone was demonstrated with a higher oxidative stress-scavenging properties than other APDs in several aspects, such as generated bulk glutathione, low HNE, and protein carbonyl productions. Contradictorily,

olanzapine, at 24 h, also enhanced HNE and protein carbonyl productions, which may underlie its induced cytotoxicity.

Different APDs exhibit variations against different stressors. Paliperidone might be useful not HA-1077 molecular weight only in alleviating oxidative stress induced by A beta(25-35) and MPP+ but also in providing neuroprotection against hydrogen peroxide.”
“Preclinical data suggest a possible role for 5-HT6 receptors in depression and anxiety. However, the results of pharmacological studies are equivocal since both blockade and stimulation of 5-HT6 receptors may evoke antidepressant- and anxiolytic-like effects.

In the present study, the effects of the 5-HT6 receptor agonist EMD 386088, administered intrahippocampally (i.hp.) to rats, were assessed in behavioral tests commonly used for evaluating antidepressant- and anxiolytic-like activities.

EMD 386088 (10 and 20 mu g, i.hp.) exerted a significant antidepressant-like effect as revealed by decreased duration of rats’ immobility in the forced swim test. This effect was blocked by systemic administration of the selective 5-HT6 receptor antagonist SB-399885.