Guyot M C, Palfi S, Stutzmann J M, Mazière M, Hantraye P, Brouillet E
Service Hospitalier Frédéric Joliot, Unité de Recherche Associée 2210 Commissariat à l'Energie Atomique-Centre National de la Recherche Scientifique, Département de Recherche Médicale, Orsay, France.
Neuroscience. 1997 Nov;81(1):141-9. doi: 10.1016/s0306-4522(97)00192-9.
The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.
在由3-硝基丙酸（一种琥珀酸脱氢酶的不可逆抑制剂）长期治疗（腹腔注射三周）诱导的进行性纹状体神经变性大鼠模型中，研究了利鲁唑假定的神经保护作用。运动行为的定量分析表明，利鲁唑（8毫克/千克/天）对3-硝基丙酸诱导的运动缺陷具有显著的保护作用（60%），这是通过两项独立的运动测试评估得出的。此外，对3-硝基丙酸诱导的损伤进行定量分析表明，3-硝基丙酸产生的纹状体损伤体积显著减少了84%，这种神经保护作用在纹状体后部和苍白球中似乎更为明显。此外，还证实利鲁唑对全身性3-硝基丙酸的这种神经保护作用并非源于神经毒素生物利用度的降低或利鲁唑对3-硝基丙酸诱导的琥珀酸脱氢酶抑制的直接作用。我们发现，利鲁唑使立体定向纹状体内注射丙二酸（一种可逆的琥珀酸脱氢酶抑制剂）产生的纹状体损伤大小显著减少了48%。此外，利鲁唑给药并未改变全身性3-硝基丙酸诱导的皮质和纹状体琥珀酸脱氢酶活性的抑制。目前的结果与利鲁唑对肌萎缩侧索硬化有益作用一致，表明该化合物可能对慢性神经退行性疾病的治疗有用。
