Migler B M, Warawa E J, Malick J B
ICI Pharmaceuticals Group, Department of Chemistry, ICI Americas Inc., Wilmington, DE 19897.
Psychopharmacology (Berl). 1993;112(2-3):299-307. doi: 10.1007/BF02244925.
Seroquel was compared to clozapine and several other antipsychotic agents in tests predictive of antipsychotic activity or extrapyramidal symptoms. In the conditioned avoidance test in squirrel monkeys as well as several paradigms using apomorphine or amphetamine-induced behavioral alterations, seroquel displayed the profile of a drug with potential antipsychotic activity. In these paradigms the potency of seroquel was somewhat less than clozapine in rodent tests, while the reverse was true in higher species, i.e. monkeys, cats. In tests designed to evaluate the propensity to induce EPS or tardive dyskinesia, for example, the production of dyskinetic reactions in haloperidol-sensitized cebus monkeys, seroquel displayed a profile similar to clozapine and disparate from typical antipsychotic drugs. In drug-naive cebus monkeys seroquel sensitized significantly fewer monkeys than haloperidol and the dyskinetic reactions were of significantly less intensity. It is anticipated that this novel antipsychotic agent will have a significantly reduced propensity to produce extrapyramidal symptoms and tardive dyskinesia than typical antipsychotics.
在预测抗精神病活性或锥体外系症状的试验中,将思瑞康与氯氮平和其他几种抗精神病药物进行了比较。在松鼠猴的条件性回避试验以及使用阿扑吗啡或苯丙胺诱导行为改变的几种范例中,思瑞康表现出具有潜在抗精神病活性药物的特征。在这些范例中,在啮齿动物试验中思瑞康的效力略低于氯氮平,而在高等物种(即猴子、猫)中情况则相反。例如,在旨在评估诱导EPS或迟发性运动障碍倾向的试验中,在氟哌啶醇致敏的卷尾猴中产生运动障碍反应,思瑞康表现出与氯氮平相似的特征,与典型抗精神病药物不同。在未用药的卷尾猴中,思瑞康使猴子致敏的数量明显少于氟哌啶醇,且运动障碍反应的强度明显较小。预计这种新型抗精神病药物产生锥体外系症状和迟发性运动障碍的倾向将比典型抗精神病药物显著降低。