Goldstein J M, Litwin L C, Sutton E B, Malick J B
Department of Pharmacology ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, DE 19897.
Psychopharmacology (Berl). 1993;112(2-3):293-8. doi: 10.1007/BF02244924.
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.
采用细胞外单单位记录技术,在可能预测抗精神病药物(AP)活性的电生理试验中,比较了思瑞康与参比抗精神病药物氯氮平和氟哌啶醇的作用。在逆转d-苯丙胺对中脑边缘系统(A10)而非黑质纹状体(A9)含多巴胺(DA)神经元的抑制作用方面,思瑞康和氯氮平的活性存在差异,前者更为显著,而氟哌啶醇则表现出相反的选择性。在细胞群体研究中,思瑞康和氯氮平的急性治疗选择性地增加了自发活动的A10 DA细胞数量,发现这与这两种药物在重复(28天)给药后导致A10 DA细胞去极化失活(DI)的能力相关。这种活性特征与氟哌啶醇不同,氟哌啶醇急性给药会导致A9和A10 DA活性细胞数量非选择性增加,且与该药物在重复治疗后导致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,思瑞康与氯氮平类似,可能是一种产生EPS/TD可能性降低的非典型AP。