Casey D E
Psychiatry Service, VA Medical Center, Portland, OR 97207, USA.
Psychopharmacology (Berl). 1996 Mar;124(1-2):134-40. doi: 10.1007/BF02245613.
Extrapyramidal side effects (EPS) are major limitations to neuroleptic treatment of psychoses. To evaluate further the behavioral characteristics of the novel antipsychotic agents, a wide range of single intramuscular doses of sertindole (0.1-2.5 mg/kg IM), risperidone (0.01-0.25 mg/kg IM), clozapine (1.0-25.0 mg/kg IM), and haloperidol (0.01-0.25 mg/kg IM) were blindly evaluated at weekly intervals in Cebus monkeys previously sensitized to neuroleptics. All drugs except clozapine produced dystonia and parkinsonian symptoms, but haloperidol and risperidone were 50-100 times more potent than sertindole in producing EPS. Sertindole, risperidone and haloperidol had no significant sedative effects, whereas clozapine produced dose related sedation. Risperidone, clozapine and haloperidol but not sertindole decreased locomotor activity. Sertindole, risperidone and clozapine had a calming effect at doses below the EPS threshold, unlike haloperidol. Sertindole has many behavioral effects in nonhuman primates that are similar to those seen with the new antipsychotics, risperidone and clozapine, which suggests a favorable antipsychotic benefit/risk ratio in the clinic, especially regarding EPS.
锥体外系副作用（EPS）是精神病患者使用抗精神病药物治疗的主要限制因素。为了进一步评估新型抗精神病药物的行为特征，在预先对神经阻滞剂敏感的卷尾猴中，每周对多种单剂量肌肉注射的舍吲哚（0.1 - 2.5mg/kg，肌肉注射）、利培酮（0.01 - 0.25mg/kg，肌肉注射）、氯氮平（1.0 - 25.0mg/kg，肌肉注射）和氟哌啶醇（0.01 - 0.25mg/kg，肌肉注射）进行盲法评估。除氯氮平外，所有药物均产生了肌张力障碍和帕金森氏症状，但在产生EPS方面，氟哌啶醇和利培酮的效力比舍吲哚强50 - 100倍。舍吲哚、利培酮和氟哌啶醇没有明显的镇静作用，而氯氮平产生了与剂量相关 的镇静作用。利培酮、氯氮平和氟哌啶醇降低了运动活性，但舍吲哚没有。与氟哌啶醇不同，舍吲哚、利培酮和氯氮平在低于EPS阈值的剂量下具有镇静作用。舍吲哚在非人类灵长类动物中具有许多行为效应，与新型抗精神病药物利培酮和氯氮平相似;这表明在临床上具有良好的抗精神病效益/风险比，特别是在EPS方面。
