Smith Judith A, Goudie Andrew J
Department of Psychology, Liverpool University, United Kingdom.
Exp Clin Psychopharmacol. 2002 Nov;10(4):376-84. doi: 10.1037//1064-1297.10.4.376.
Rats discriminated the novel antipsychotic quetiapine (Seroquel). Full generalization was seen with the novel ("atypical") antipsychotics, clozapine, olanzapine, and risperidone. Generalization was not seen with the older "typical" antipsychotics, haloperidol, chlorpromazine, and loxapine, or with the novel atypical antipsychotic, amisulpride. The pattern of generalization resembled that seen in rats trained to discriminate a low dose (1.25 mg/kg) of clozapine, which dissociates most novel antipsychotics from typical antipsychotics. However, the failure of the novel antipsychotic amisulpride to generalize demonstrates that this bioassay does not detect all novel antipsychotics. These data suggest that the discrimination of antipsychotics such as quetiapine may be of value in the development of novel antipsychotics, although the relationship between the discriminative properties of such drugs and their clinical actions is unclear.
大鼠能够区分新型抗精神病药物喹硫平(思瑞康)。新型(“非典型”)抗精神病药物氯氮平、奥氮平和利培酮出现了完全泛化现象。而传统的“典型”抗精神病药物氟哌啶醇、氯丙嗪和洛沙平,以及新型非典型抗精神病药物阿立哌唑则未出现泛化现象。泛化模式类似于在经训练区分低剂量(1.25毫克/千克)氯氮平的大鼠中所观察到的情况,氯氮平能将大多数新型抗精神病药物与典型抗精神病药物区分开来。然而,新型抗精神病药物阿立哌唑未能泛化,这表明该生物测定法无法检测到所有新型抗精神病药物。这些数据表明,对喹硫平这类抗精神病药物的区分在新型抗精神病药物的研发中可能具有价值,尽管此类药物的辨别特性与其临床作用之间的关系尚不清楚。