非定型抗精神病薬リスペリドンの中枢ドーパミン放出に対する効果の1検討
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概要
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New classes of medicines, which are called as atypical antipsychotics, have recently been introduced for the medical therapy of schizophrenic patients. Respecting their abilities to block the central serotonergic receptor (5-HT^<2A>on the neurons releasing dopamine), these medicines may conceivably affect the activities of dopaminergic system, i.e., principal targets of conventional antipsychotic medicines such as haloperidol. The present study was undertaken to investigate how a new class of medicine, risperidone, affects the real discharge of dopamine from nerve endings comparing to the conventional typical anti-psychotics, haloperidol, in the multiple brain areas, for example, striatum, nucleus accumbens, and forebrain. In order to induce the dopamine release, we utilized microdialysis methods and perfused p-chroloamphetamine, which was dissolved in saline,at a dose of 0.02 mol. And the amounts of dopamine released into perfusates through brain dialysis probe were measured. Then the effects on the forced release of dopamine were compared between haloperidole (0.5 mg/kg) and risperidone (0.5 mg/kg). The present study clearly showed the contradictory results for two different classes of medicines. Haloperidol apparently depressed the dopamine release by approximately 50% of that observed before the injection, in all areas studied, whereas risperidone rather increased by 20%, especially in the forebrain. These results may well explain the effectiveness of new class medicines in eliminating the negative symptoms of schizophrenia, and their reducing ability against the appearance of extra-pyramidal side effects, because these symptoms. And side effects have been considered as results, caused by the shortage of dopamine in each responsible brain area.
- 愛知医科大学の論文
- 2005-03-10