Chlorpromazine, clozapine and olanzapine inhibit anionic amino acid transport in cultured human fibroblasts
| Autor: | Ovidio Bussolati, Massimiliano G. Bianchi, Valeria Dall'Asta, C. Maggini, Bianca Maria Rotoli, G. C. Gazzola, C. Marchesi |
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| Rok vydání: | 2006 |
| Předmět: |
Olanzapine
Amino Acid Transport Systems Acidic Chlorpromazine medicine.medical_treatment Clinical Biochemistry Pharmacology Biochemistry Benzodiazepines medicine Haloperidol Humans Amino Acids Antipsychotic Clozapine Cells Cultured chemistry.chemical_classification Chemistry Organic Chemistry Glutamate receptor Biological Transport Fibroblasts Amino acid Glutamine Antipsychotic Agents medicine.drug |
| Zdroj: | Amino Acids. 31:93-99 |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-006-0312-3 |
| Popis: | We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated by system X(-) (AG) (EAAT transporters) in cultured human fibroblasts. With 30 microM chlorpromazine, transport inhibition is detectable after 3 h of treatment, maximal after 48 h (60%), and referable to a decrease in V(max). Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X(-) (AG) since transport systems A and y(+) are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines, clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective. Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic patients. |
| Databáze: | OpenAIRE |
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