Megens A A, Awouters F H, Niemegeers C J
Department of Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Psychopharmacology (Berl). 1988;95(4):493-6. doi: 10.1007/BF00172961.
Risperidone, a new antipsychotic agent, was studied for its effects on spontaneous motor activity in rats in comparison with haloperidol. Motor activity was recorded via the optical scanning technique (horizontal and vertical activity) and via a recently developed technique based on the piezo-electric principle which, in contrast to optical scanning, is very sensitive to small, stationary movements (piezo activity). Risperidone and haloperidol at low doses depressed both vertical activity (ED50s: 0.062 and 0.038 mg/kg, respectively) and horizontal activity (0.18 and 0.060 mg/kg, respectively). With increase of dose, motor activity decline was significantly faster with haloperidol than with risperidone. Moreover, haloperidol also rapidly depressed piezo activity (ED50: 0.085 mg/kg) whereas risperidone depressed this component of motor behaviour at much higher doses only (ED50: 2.80 mg/kg). Visual inspection did not reveal abnormal behavioural movements following the test compounds. Risperidone, therefore, preserves normal small movements over a much larger dose interval than haloperidol; this effect may be related to its relatively low cataleptogenic activity and potentially also to a reduced EPS liability. The present results further confirm that the piezo technique may complement the optical scanning method, and thereby enhance the information on the extent that test compounds modify behaviour.
将新型抗精神病药物利培酮与氟哌啶醇进行比较,研究其对大鼠自发运动活性的影响。通过光学扫描技术(水平和垂直活性)以及基于压电原理的最新技术记录运动活性,与光学扫描不同,该技术对微小的静止运动非常敏感(压电活性)。低剂量的利培酮和氟哌啶醇均降低垂直活性(ED50分别为0.062和0.038mg/kg)和水平活性(分别为0.18和0.060mg/kg)。随着剂量增加,氟哌啶醇使运动活性下降的速度明显快于利培酮。此外,氟哌啶醇还迅速降低压电活性(ED50:0.085mg/kg),而利培酮仅在高得多的剂量下才降低运动行为的这一成分(ED50:2.80mg/kg)。肉眼观察未发现受试化合物后出现异常行为动作。因此,与氟哌啶醇相比,利培酮在更大的剂量范围内能保持正常的微小运动;这种效应可能与其相对较低的致僵活性有关,也可能与降低的锥体外系反应倾向有关。目前的结果进一步证实,压电技术可补充光学扫描方法,从而增加有关受试化合物改变行为程度的信息。