Activity of ''seroquel'' (ICI204,636) in animal models for atypical properties of antipsychotics: A comparison with clozapine
Activity of ''seroquel'' (ICI204,636) in animal models for atypical properties of antipsychotics: A comparison with clozapine
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DOI：
10.1016/0893-133x(96)00001-2
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发表时间：
1996-10-01
影响因子：
7.6
通讯作者：
Cools, AR
中科院分区：
文献类型：
--
作者：
Ellenbroek, BA;Lubbers, LJ;Cools, AR
精神分裂症的药物治疗仍然存在两个主要问题：（1）大多数抗精神病药物仍然引起严重的神经系统（锥体外系）副作用;（2）很少有抗精神病药物有效治疗精神分裂症的阴性症状。在本研究中，我们评估了ICI 204，636在大鼠爪试验和安非他明诱导的猴子社会隔离中的作用，并将其与氯氮平的作用进行了比较。爪试验已被证明是区分经典和非典型精神抑制药物的有效模型。猴子社会隔离模型似乎代表了少数几个对精神分裂症阴性症状有效的动物模型之一。结果表明ICI 204，636和氯氮平在爪试验中均具有非典型抗精神病药的特征，表明在人类中诱导锥体外系副作用的倾向降低。同样，ICI 204，636和氯氮平被发现可以防止安非他明诱导的猴子社会隔离，这表明对减轻精神分裂症的阴性症状有良好的治疗效果。总体而言，数据表明ICI 204，636可能是一种新的有趣的抗精神病药物，与氯氮平非常相似。
The pharmacologic treatment of schizophrenia still suffers from two major problems: (1) most antipsychotic drugs still induce severe neurologic (extrapyramidal) side effects; (2) few antipsychotic drugs are effective in treating the negative symptoms of schizophrenia. In the present study, we have evaluated the effects of ICI 204,636 in the rat paw test and the amphetamine-induced social isolation in monkeys and compared them with the effects of clozapine. The paw test has been shown to be a valid model for differentiating classic and atypical neuroleptic drugs. The monkey social isolation model seems to represent one of the few animal models with validity for the negative symptoms of schizophrenia. The results show that both ICI 204,636 and clozapine had the profile of an atypical antipsychotic in the paw test, suggesting a reduced propensity to induce extrapyramidal side effects in humans. Likewise, ICI 204,636 and clozapine were found to prevent the amphetamine-induced social isolation in monkeys, suggesting a good therapeutic effect mitigating the negative symptoms in schizophrenia. Overall, the data suggest that ICI 204,636 may present a new and interesting antipsychotic drug, closely resembling clozapine.