Clozapine, agranulocytosis, and benign ethnic neutropenia

Postgraduate medical journal (Impact Factor: 1.55). 10/2005; 81(959):545-6. DOI: 10.1136/pgmj.2004.031161
Source: PubMed
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    ABSTRACT: The immunomodulatory effects of clozapine (CLZ), antipsychotic drug, were investigated in vivo using female Balb/c mice. The main aim of this study was to evaluate the immunomodulatory effects of CLZ, antipsychotic drug, following daily intraperitoneal injection to female Balb/c mice over a period of 21 days. Mice were divided into five groups, eight animals per group. Group I, served as a control group, received only the vehicle. Groups II-V received a daily intraperitoneal dose of CLZ (1, 5, 10 and 20 mg/kg, respectively) over a period of 21 days. CLZ has shown a significant decrease in the animal body weight, and it showed a significant decrease in the percentage of circulating neutrophils and lymphocytes while circulating monocytes were increased. The immunotoxicity has been also assessed by evaluating spleen cellularity, humoral immune response to a foreign antigen using sheep red blood cells and delayed-type hypersensitivity reaction. The results showed a marked suppression in these responses in CLZ-treated mice compared with the control group. Detectable changes have also been noticed in the histology of the footpad tissue and spleen. Results showed significant immunomuodulatory effects of CLZ when used in Balb/c mice.
    12/2013; DOI:10.1111/jphp.12150
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    ABSTRACT: Antipsychotic drugs (APDs) have been used to ease the symptoms of schizophrenia. APDs have recently been reported to regulate the immune response. Our previous studies revealed that the atypical APDs risperidone and clozapine and the typical APD haloperidol can inhibit the phagocytic ability of macrophages. Our research next determined the effects of APDs on the phagocytic ability of neutrophils, which are the most abundant type of white blood cells in mammals. Here we provide evidence that clozapine and haloperidol can induce increased phagocytic uptake of Escherichia coli by differentiated HL-60 cells and by purified human neutrophils. Furthermore, clozapine and haloperidol can increase the myeloperoxidase activity and IL-8 production in neutrophils. Our results also show that clozapine can inhibit E. coli survival within differentiated HL-60 cells. Furthermore, clozapine and haloperidol are shown to enhance cell surface Mac-1 expression and the activated AKT signaling pathway in purified neutrophils exposed to E. coli. These results indicate that clozapine and haloperidol can increase the phagocytic ability of neutrophils by increasing AKT activation when cells are exposed to bacteria. Copyright © 2014 Elsevier B.V. All rights reserved.
    International Immunopharmacology 12/2014; 23(2):550-7. DOI:10.1016/j.intimp.2014.09.030 · 2.71 Impact Factor
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    ABSTRACT: Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5-10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.
    CNS spectrums 08/2014; 19(4):279-81. DOI:10.1017/S1092852914000418 · 1.30 Impact Factor