A STUDY ON CLASSIFICATION OF ANTIPSYCHOTIC DRUGS BY MEANS OF THEIR ABILITY TO INDUCE THE RELEASE OF NEUROTRANSMITTERS

1.本研究采用微透析技术建立了大鼠内侧前额叶皮层细胞外谷氨酸水平的实时监测方法，并研究了不同类型抗精神病药物对前额叶谷氨酸释放的影响。非典型抗精神病药物（如氯氮平、奥氮平和利培酮）至少服用一次，但典型抗精神病药物氟哌啶醇不能减弱K^+诱导的内侧前额叶皮层细胞外谷氨酸水平升高。这一发现表明，急性服用非典型抗精神病药物可能会抑制前额叶皮层神经元的活动。由于非典型抗精神病药物选择性衰减的即时早期基因弧的表达，在内侧前额叶皮层和苯环己哌啶治疗的大鼠，精神分裂症的动物模型可能是有用的阐明这些药物的作用部位。然而，多巴胺能神经传递的改变可能并不有助于 ...更多信息 o非典型抗精神病药物减弱苯环己哌啶诱导的ARC表达的作用机制.结合其他实验室的报告，急性给予氯氮平、利培酮和奥氮平可增加大鼠前额叶皮质多巴胺、去甲肾上腺素和乙酰胆碱的释放。这些非典型抗精神病药物至少在一次给药时可减少前额谷氨酸的释放，而利培酮可促进5-羟色胺的释放，但氯氮平或奥氮平则不然。氟哌啶醇可能对前额叶神经递质的释放影响甚微。根据抗精神病药物能诱导多巴胺、去甲肾上腺素和乙酰胆碱的区域特异性释放，可将其分为三大类：I.以前额型为主，如氯氮平，II.非优势前额型如利培酮，III.主要为皮质下型，如氟哌啶醇。前两类抗精神病药在临床上是非典型的，而第二类药物在高剂量时缺乏其特异性。少

1. We established the in vivo method of monitoring in real-time extracellular glutamate levels in rat medial prefrontal cortex by employing the microdialysis technique and then examined the effect of different types of antipsychoic drugs on prefrontal glutamate release. The atypical antipsychotic drugs such as clozapine, olanzapine and risperidone at at least one dose, but not the typical antipsychotic haloperidol, attenuated high K^+-induced extracellular glutamate levels in the medial prefrontal cortex. This finding suggests that acute administration of atypical antipsychotics may inhibit prefrontal glutamatergic activity.2. Since atypical antipsychotic drugs selectively attenuated the expression of the immediate-early gene arc in the medial prefrontal cortex and nucleus accumbens of phencyclidine-treated rats, this animal model of schizophrenia may be useful for elucidating the sites of action of these drugs. However, alteration of dopaminergic neurotransmission may not contribute t … More o the mechanism of action of atypical antipsychotic drugs in regard to their ability to attenuate phencyclidine-induced arc expression.3. Taken together with previous reports from other laboratories, acute administration of clozapine, risperidone and olanzapine may increase the release of dopamine, norepinephrine and acetylcholine in rat prefrontal cortex. These atypical antipsychotics may decrease prefrontal glutamate release at at least one dose, whereas risperidone, but not clozapine or olanzapine, may facilitate serotonin release. Haloperidol may have minimal effect on the prefrontal release of either neurotransmitters.4. By means of the ability to induce the region-specific release of dopamine, norepinephrine and acetylcholine, antipsychotic drugs may be classified into three types: I. dominantly prefrontal type such as clozapine, II. Non-dominantly prefrontal type such as risperidone, and III. Dominantly subcortical type such as haloperidol. The former two types are atypical antipsychotics in regard to the clinical effects, although the type II drugs at high doses lack their atypicality. Less