Long-Term Effects of Olanzapine, Risperidone, and Quetiapine on Ionotropic Glutamate Receptor Types: Implications for Antipsychotic Drug Treatment
| Autor: | Nora S. Kula, Kehong Zhang, Frank I. Tarazi, Ross J. Baldessarini |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Olanzapine Dibenzothiazepines Kainic acid medicine.drug_class Atypical antipsychotic AMPA receptor Pharmacology Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Benzodiazepines Quetiapine Fumarate chemistry.chemical_compound Receptors Kainic Acid Animals Medicine Receptors AMPA business.industry Pirenzepine Risperidone Rats Receptors Glutamate nervous system chemistry Molecular Medicine Ionotropic glutamate receptor Quetiapine business Antipsychotic Agents Ionotropic effect medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 306:1145-1151 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Levels of ionotropic glutamate (Glu) N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainic acid (KA) receptors in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after continuous treatment for 28 days with the atypical antipsychotics olanzapine, risperidone, and quetiapine, or vehicle controls. All three treatments significantly decreased NMDA binding in caudate-putamen (CPu; by 30, 34, and 26%, respectively) but increased AMPA receptor levels in same region (by 22, 30, and 28%). Olanzapine and risperidone, but not quetiapine, also reduced NMDA receptor labeling in hippocampal CA1 (21 and 19%) and CA3 (23 and 22%) regions. KA receptors were unaltered by any treatment in the brain regions examined. These findings suggest that the antipsychotic effects of olanzapine and risperidone may be mediated in part by NMDA receptors in hippocampus, and perhaps AMPA receptors in CPu. The findings also support the hypothesis that down-regulation of NMDA receptors by atypical antipsychotic agents in CPu contributes to their low risk of extra-pyramidal side effects. Inability of olanzapine, risperidone, and quetiapine to alter KA receptors suggests their minimal role in mediating the central nervous system actions of these drugs. |
| Databáze: | OpenAIRE |
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