Miklya Ildikó
Semmelweis University, Department of Pharmacology and Pharmacotherapy, Budapest, Hungary.
Pharmacol Rep. 2014 Jun;66(3):453-8. doi: 10.1016/j.pharep.2013.11.003. Epub 2014 Apr 3.
(-)-Deprenyl and rasagiline are classified as selective inhibitors of B-type MAO. The DATATOP study revealed that the administration of (-)-deprenyl to untreated patients with Parkinson's disease (PD) significantly delays the need for levodopa therapy (Parkinson Study Group, 1989). Rasagiline was ineffective in this respect (Parkinson Study Group, 2002). The aim of this paper is to explain the reasoning behind the differentiation between (-)-deprenyl and rasagiline.
In the shuttle box the acquisition of a two way conditioned avoidance response (CAR) was analyzed on male Wistar rats during 5 consecutive days. Tetrabenazine-treatment (1mg/kg sc) depletes the transmitters from their stores in the nerve terminals of the catecholaminergic neurons and blocks the acquisition of a CAR. Catecholaminergic activity enhancer (CAE) substances [(-)-deprenyl, (-)-BPAP] fully antagonize the tetrabenazine-induced learning deficit. Using (-)-deprenyl and (-)-BPAP as reference substances, we measured the effect of rasagiline and J-508 in this test. Rasagiline is the desmethyl-analog of J-508, described by Knoll in 1978.
In contrast to (-)-deprenyl and (-)-BPAP, J-508 and rasagiline were found in the shuttle box test to be devoid of the CAE effect.
Since convincing experimental and clinical evidence speaks in favor for the conclusion that the catecholaminergic activity enhancer (CAE) effect of (-)-deprenyl is responsible for the significantly delayed need for levodopa therapy in untreated patients with PD (Knoll, 2012) and rasagiline is devoid of the CAE effect, this might explain why "...based on current evidence, rasagiline cannot be said to definitely have a disease-modifying effect" [Robottom, 2011].
（-）-司来吉兰和雷沙吉兰被归类为B型单胺氧化酶的选择性抑制剂。DATATOP研究表明，给未经治疗的帕金森病（PD）患者服用（-）-司来吉兰可显著延迟左旋多巴治疗的需求（帕金森研究组，1989年）。雷沙吉兰在这方面无效（帕金森研究组，2002年）。本文旨在解释（-）-司来吉兰和雷沙吉兰之间差异背后的推理。
在穿梭箱中，连续5天对雄性Wistar大鼠双向条件回避反应（CAR）的习得进行分析。丁苯那嗪治疗（1mg/kg皮下注射）会耗尽儿茶酚胺能神经元神经末梢中递质的储存，并阻断CAR的习得。儿茶酚胺能活性增强剂（CAE）物质[（-）-司来吉兰、（-）-BPAP]可完全拮抗丁苯那嗪诱导的学习缺陷。以（-）-司来吉兰和（-）-BPAP作为参考物质，我们在该试验中测量了雷沙吉兰和J-508的作用。雷沙吉兰是J-508的去甲基类似物，由Knoll于1978年描述。
与（-）-司来吉兰和（-）-BPAP相反，在穿梭箱试验中发现J-508和雷沙吉兰没有CAE效应。
由于有令人信服的实验和临床证据支持以下结论，即（-）-司来吉兰的儿茶酚胺能活性增强剂（CAE）效应是未经治疗的PD患者左旋多巴治疗需求显著延迟的原因（Knoll，2012年），而雷沙吉兰没有CAE效应，这可能解释了为什么“……基于目前的证据，不能肯定地说雷沙吉兰具有疾病修饰作用”[Robottom，2011年]。
