Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.

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Heiser P, Schulte E, Hausmann C, Becker R, Remschmidt H, Krieg JC, Vedder H

Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):297-302.

PubMed ID

14751426 [ View in PubMed

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Abstract

PURPOSE: The goal of the present study was to determine the effects of clozapine (Cloz) and its metabolites norclozapine (Norcloz) and clozapine-N-oxide (Cloz-N-oxide) on the 5-HT(2) receptor system on the levels of protein and gene expression in in vitro systems of primary cortical cells of the rat and human hippocampal SHS5Y5 neuroblastoma cells. METHODS: Clinically relevant concentrations of Cloz (200/400 ng/ml) and its metabolites (200 ng/ml) were used for the examination of the effects of Cloz and its metabolites on serotoninergic 5-HT(2) receptor parameters (density, affinity and mRNA levels) as well as on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels in primary cortical cells of the rat after treatment for 24 h under in vitro conditions. To compare the results to human cells, we also measured treatment-induced changes in 5-HT(2) and GAPDH mRNA levels in human hippocampal SHS5Y5 cells. RESULTS: A significant decrease was found in primary cortical cells for 5-HT(2) receptor density (Cloz 200/Cloz 400/Norcloz 200 and Cloz-N-oxide 200 vs. control) and 5-HT(2A) receptor mRNA levels (Cloz 200 vs. control). 5-HT(2A) receptor mRNA levels were also significantly reduced (Norcloz 200 vs. control) in SHS5Y5 cells. GAPDH mRNA levels were not affected. CONCLUSIONS: The results of the present study show that Cloz and Norcloz induce significant alterations on the 5-HT(2) receptor system in primary cortical cells of the rat and in human hippocampal cells.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clozapine	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details