Atypical antipsychotic effects of quetiapine fumarate in animal models  

富马酸奎的平在动物模型中的非典型抗精神病作用(英文)

作　　者：管瀚俊[1] 戴今 朱兴族 

机构地区：[1]中国科学院上海药物研究所药理一室

出　　处：《Acta Pharmacologica Sinica》2000年第3期15-20,共6页中国药理学报（英文版）

摘　　要：AIM: To evaluate the effect of quetiapine fumarate in animal models of schizophrenia and its possibility to induce extrapyramidal side effects (EPSE). METHODS: The enhancement of immobility in a forced swimming test of mice induced by repeated treatment with phencyclidine and amphetamine swimming 'normalization' test of mice were used as animal models of negative and positive symptoms of schizophrenia, respectively. The paw test of rats was used to evaluate the possibility by quetiapine fumarate to induce EPSE. RESULTS: After treatment with phencyclidine (10mg·kg-1·d-1, sc, 14 d), the immobility time in the forced swimming test of mice was increased (P <0.0l). Quetiapine fumarate (20, 40, and 80 mg·kg-1, ig) and clozapine (10 and 30 mg·kg-1, ig) attenuated the enhanced immobility in the forced swimming test induced by repeated treatment with phencyclidine (P<0.01), whereas haloperidol (0.3 and 1 mg·kg-1, ig) had no effect. In amphetamine swimming 'normalization' test, quetiapine fumarate ameliorated the disorder induced by amphetamine in a dose-dependent manner. In paw test, quetiapine fumarate was much less effective in increasing the forelimb retraction time (FRT) than the hindlimb retraction time (HRT). The minimal effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) of quetiapine fumarate was 20 mg·kg-1 and 100 mg·?kg-1, respectively, and the ratio of MEDFRT to MEDHRT was 5. CONCLUSION: The effects of quetiapine fumarate in these models indicated its clinical effect on schizophrenia with a reduced liability to produce EPSE.目的:评价富马酸奎的平在精神分裂症阴性和阳性症状模型中的作用及导致锥体外系副反应(EPSE)的可能性。方法:以苯环利啶(10mg·kg^(-1)·d^(-1),sc,14d)引起小鼠在强制性游泳实验中保持不动的时间(immobility time,IT)延长为阴性症状模型,d-苯丙胺游泳正常化实验为阳性症状模型,paw test评价药物导致EPSE的可能性。结果:富马酸奎的平(20,40,80mg·kg^(-1),ig)可逆转苯环利啶引起的小鼠在强制性游泳实验中IT延长;5-80mg·kg^(-1),ig可对抗d-苯丙胺导致的小鼠游泳行为异常;在paw test中更易使后肢回缩时间延长,MED_(FRT)/MED_(HRT)比值为5。结论:富马酸奎的平是对精神分裂症阴性和阳性症状均有效的非典型抗精神病药物。

关 键 词：quetiapine fumarate CLOZAPINE HALOPERIDOL antipsychotic agents PHENCYCLIDINE SWIMMING depression schizophrenia and disorders with psychotic features basal ganglia diseases 

分 类 号：R96[医药卫生—药理学]