SEROQUEL - ELECTROPHYSIOLOGICAL PROFILE OF A POTENTIAL ATYPICAL ANTIPSYCHOTIC
SEROQUEL - ELECTROPHYSIOLOGICAL PROFILE OF A POTENTIAL ATYPICAL ANTIPSYCHOTIC
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DOI：
10.1007/bf02244924
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发表时间：
1993-09-01
影响因子：
3.4
通讯作者：
MALICK, JB
中科院分区：
文献类型：
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作者：
GOLDSTEIN, JM;LITWIN, LC;MALICK, JB
采用细胞外单单位记录技术比较思瑞康与参考抗精神病（AP）药物氯氮平和氟哌啶醇在电生理试验中的作用，这些试验可以预测AP活性。思瑞康和氯氮平的差异更积极地扭转d-苯丙胺对中脑边缘（A10）比黑质纹状体（A9）多巴胺（DA）含神经元的抑制作用，而氟哌啶醇表现出相反的选择性。在细胞群研究中，急性治疗seroquel和氯氮平选择性地增加了自发活动的A10 DA细胞的数量，这被发现与这两种药物的能力，导致去极化失活（DI）的A10 DA细胞后，重复（28天）的管理。这种活性特征与氟哌啶醇不同，氟哌啶醇急性引起活性A9和A10 DA细胞数量的非选择性增加，这与该药物在重复处理后引起A9和A10 DA细胞DI的能力有关。由于A10 DA细胞的DI可能与AP疗效相关，而A9 DA细胞的DI可能预测AP引起锥体外系副作用（EPS）和迟发性运动障碍（TD）的能力，因此seroquel与氯氮平一样，可能是一种非典型AP，产生EPS/TD的可能性降低。
Extracellular single unit recording techniques were employed to compare the effects of seroquel with the reference antipsychotic (AP) agents clozapine and haloperidol in electrophysiological tests that may predict AP activity. Seroquel and clozapine were differentially more active in reversing the inhibitory actions of d-amphetamine on mesolimbic (A10) than nigrostriatal (A9) dopamine (DA)-containing neurons, whereas haloperidol exhibited the opposite selectivity. In cell population studies, acute treatment with seroquel and clozapine selectively increased the number of spontaneously active A10 DA cells, which was found to correlate with the ability of both these drugs to cause depolarization inactivation (DI) of A10 DA cells following repeated (28 day) administration. This profile of activity was unlike that of haloperidol, which acutely caused a nonselective increase in the number of active A9 and A10 DA cells, associated with the ability of this agent to cause DI of both A9 and A10 DA cells after repeated treatment. Since DI of A10 DA cells may be correlated with AP efficacy whereas DI of A9 DA cells may predict the ability of an AP to cause extrapyramidal side effects (EPS) and tardive dyskinesia (TD), seroquel, like clozapine, may be an atypical AP with a reduced likelihood for producing EPS/TD.