Molecular mechanisms of anti-psychotic drugs for improvement of cancer treatment.

Anti-psychotic medications are widely used to treat schizophrenia and bipolar disorder. Besides their medical applications, anti-psychotic drugs have other pharmacological properties which are involved in multiple intracellular functions including metabolism, cell stress, cell-cycle regulation, survival and apoptosis through modulation of cellular signaling pathways such as PI3K/Akt/GSK-3ß, STAT3 and wingless (Wnt)-related intracellular signaling. Also, anti-psychotics counteract the growth of tumor cells by stimulating the cellular immune system and natural killer cells. On the other hand, the positive charge and the lipophilicity of anti-psychotics have significant roles in the inhibition of P-gp pumps resulting in accumulation of chemotherapy drugs as well as increasing the cellular susceptibility to chemotherapy, autophagy, angiogenesis inhibition, stem cells differentiation induction and changing the expression of tumor suppressor genes and oncogenes. Overall, anti-psychotics are able to inhibit the proliferation of cancer cells through modulation of different cellular pathways. Anti-psychotics act as anti-cancer drugs and besides can increase the efficacy of anti-cancer agents in cancer cells. In this study, the anti-cancer effects of different anti-psychotic medicines on various malignant tumor cells and their molecular mechanisms have been discussed.

Alterations in oxidative stress markers and its correlation with clinical findings in schizophrenic patients consuming perphenazine, clozapine and risperidone.

BACKGROUND AND OBJECTIVE: Today, the role of oxidative stress in development of schizophrenia has gained attention. Also, some atypical antipsychotic agents showed antioxidant properties. Therefore, in this study, we evaluated the level of oxidative stress parameters between patients treated with perphenazine, clozapine and risperidone and their relationship with schizophrenia symptoms' severity. MATERIALS AND METHODS: This was a descriptive study on 100 patients with chronic schizophrenia. Patient selection was done based on the DSM-IV-TR criteria for at least 3 months regular use of clozapine or risperidone or perphenazine and a minimum period of 2 years of schizophrenia. Ten ml of patient's blood samples were used to assess serum levels of glutathione (GSH), protein carbonyl, lipid peroxidation (LPO), superoxide dismutase (SOD) and Ferric Reducing Ability of Plasma (FRAP). Also, the severity of symptoms was assessed with the positive and negative syndrome scale (PANSS scale). P-values of less than 0.05 were considered significant. RESULTS: The results showed a significant difference between clozapine and risperidone with perphenazine in all subscales of PANSS. Also, there was a positive correlation between MDA and PANSS all subscales in risperidone and perphenazine groups and a negative correlation between MDA and PANSS in all subscales in the clozapine group. Serum level of GSH and negative symptoms in patients receiving clozapine showed a negative correlation. The results also represented that clozapine significantly increased SOD levels in comparison to perphenazine and risperidone and reduced LPO in comparison to perphenazine and risperidone, While the protein carbonyl level did not show a significant difference between three groups (p-value = 0.8). CONCLUSION: This study showed that clozapine, as an atypical antipsychotic agent, has significant antioxidant effects compared to risperidone and perphenazine. Especially, it increased SOD and GSH levels and reduced LPO in patients with schizophrenia. Therefore, clozapine's antioxidant effect may be contributive to improving negative symptoms of schizophrenic patients.

The pattern and risk factors associated with adverse drug reactions induced by Reteplase in patients with acute ST-elevation myocardial infarction: The first report from Iranian population.

OBJECTIVE: Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Reteplase is a fibrin-specific thrombolytic which is used in the treatment of AMI. There is a limited number of studies reporting the postmarketing adverse drug reactions (ADRs) induced by reteplase. This study was aimed to examine the reteplase pattern of ADR and its associated risk factors in patients with acute ST-elevation myocardial infarction. METHODS: A cross-sectional, prospective study in an 8-month period was done at the University affiliated referral cardiovascular center. The Naranjo probability scale and World Health Organization criteria for severity of ADRs were used for assessing the ADRs. The linear regression and logistic regression tests were used to evaluate the correlation between ADRs and risk factors. FINDINGS: The all 20 patients who received reteplase during the study period were entered. The majority of patients (n = 17) experienced at least one ADR. The results showed that the incidence of ADRs was mainly associated with gender and age, and the number of ADRs was associated with the history of diabetes and taking anti-diabetic agents. The gender was the main predictor in the occurrence of ADRs (odds ratio: 32, 95% confidence interval: 1.38-737.45; P = 0.030). CONCLUSION: The results showed that gender, age, diabetes mellitus, and using of anti-diabetes medications are the risk factors associated with the incidence of ADRs by reteplase.