Prat G, Pérez V, Rubi A, Casas M, Unzeta M
Laboratori de Neuropsicofarmacolgia, Institut de Recerca de L'Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
J Neural Transm (Vienna). 2000;107(4):409-17. doi: 10.1007/s007020070083.
The present study examined the effect of the highly potent and selective MAO B inhibitor PF9601N on L-DOPA-induced rotational behavior in unilateral nigrostriatal 6-hydroxydopamine lesioned rats. Three doses of PF9601N (20, 40 and 60mg/kg) were administered 30 min before an injection of L-DOPA (25mg/kg), and both contralateral and ipsilateral rotational behavior was measured. In addition, we also studied the effect produced by another MAO B inhibitor, deprenyl (20mg/kg), the MAO A inhibitor, clorgyline (20mg/kg), and the dopamine reuptake inhibitor, GBR2909 (7.5 mg/kg) on L-DOPA-induced rotational behavior. The results showed that PF9601N plus L-DOPA significantly enhanced the duration of contralateral rotational behavior with respect to L-DOPA plus vehicle in a dose-related manner. At the dose of 40 and 60mg/kg, PF9601N produced significantly more overall contralateral turning than L-DOPA plus vehicle, and at the dose of 60mg/kg, PF9601N produced significantly more turning behavior than L-DOPA plus deprenyl. These results suggest that PF9601N may be used as a novel tool in the treatment of Parkinson's disease.
本研究考察了高效选择性单胺氧化酶B(MAO B)抑制剂PF9601N对单侧黑质纹状体6-羟基多巴胺损伤大鼠左旋多巴诱导的旋转行为的影响。在注射左旋多巴(25mg/kg)前30分钟给予三种剂量的PF9601N(20、40和60mg/kg),并测量对侧和同侧的旋转行为。此外,我们还研究了另一种MAO B抑制剂司来吉兰(20mg/kg)、MAO A抑制剂氯吉兰(20mg/kg)以及多巴胺再摄取抑制剂GBR2909(7.5mg/kg)对左旋多巴诱导的旋转行为的影响。结果表明,与左旋多巴加溶媒相比,PF9601N加左旋多巴能以剂量相关的方式显著延长对侧旋转行为的持续时间。在40和60mg/kg剂量下,PF9601N产生的总体对侧旋转明显多于左旋多巴加溶媒,在60mg/kg剂量下,PF9601N产生的旋转行为明显多于左旋多巴加司来吉兰。这些结果表明,PF9601N可能作为治疗帕金森病的一种新工具。