Document Detail


Effects of haloperidol, clozapine and olanzapine on the survival of human neuronal and immune cells in vitro.
MedLine Citation:
PMID:  17881431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytotoxic effects on neuronal as well as on immune cells have been reported for both typical and atypical antipsychotic drugs. We evaluated the effects of different concentrations of a typical (haloperidol) and two atypical (clozapine, olanzapine) antipsychotics on the survival of human neuronal (SH-SY5Y cells) and immune cells (U937 cells) by determining the metabolic activity after 24 h of incubation by the modified tetrazolium method. The dopaminergic neuroblastoma SH-SY5Y and the lymphoma U-937 cell line are well established models for in vitro investigations. To further elucidate possible mechanisms of action we also determined the ATP content in the cultured cells. After experimental treatment, significant effects were detected by Kruskal Wallis test for all treatment conditions. Post-hoc tests (Dunn's method) showed that haloperidol and clozapine at the two highest concentrations (25 and 50 microg/ml) caused a significant decrease of metabolic activity in both cell systems, which was also detectable after treatment with clozapine at a concentration of 12.5 microg/ml in U937 cells. In contrast, olanzapine induced a significant increase in metabolic activity of SH-SY5Y cells at all concentrations except for the concentration of 3.1 microg/ml, whereas the metabolic activity in U937 cells was increased at concentrations of 1.6 and 6.25 microg/ml. For the determination of ATP content, the LD(50) values of the metabolic activity were used, except for olanzapine for which no distinct LD(50) value was available. Significant changes were detected for all treatments and post-hoc tests revealed that haloperidol caused a significant decrease compared to the control condition in both cell systems. These findings suggest that antipsychotic substances of different classes exert differential metabolic effects in both neuronal and immune cell systems.
Authors:
Philip Heiser; Frank Enning; Jürgen-Christian Krieg; Helmut Vedder
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-19
Journal Detail:
Title:  Journal of psychopharmacology (Oxford, England)     Volume:  21     ISSN:  0269-8811     ISO Abbreviation:  J. Psychopharmacol. (Oxford)     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-06     Completed Date:  2008-01-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8907828     Medline TA:  J Psychopharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  851-6     Citation Subset:  IM    
Affiliation:
Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Marburg, Germany. heiser@mailer.uni-marburg.de
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / analysis
Antipsychotic Agents / toxicity*
Benzodiazepines / toxicity*
Cell Line, Tumor
Cell Survival / drug effects
Clozapine / toxicity*
Dose-Response Relationship, Drug
Haloperidol / toxicity*
Humans
Monocytes / drug effects*,  metabolism
Neurons / drug effects*,  metabolism
U937 Cells
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; 12794-10-4/Benzodiazepines; 132539-06-1/olanzapine; 52-86-8/Haloperidol; 56-65-5/Adenosine Triphosphate; 5786-21-0/Clozapine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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