Boireau A, Dubédat P, Bordier F, Peny C, Miquet J M, Durand G, Meunier M, Doble A
Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Département Biologie, Vitry-sur-Seine, France.
Neuroreport. 1994 Dec 20;5(18):2657-60.
We have investigated whether riluzole, a compound that interferes with glutamatergic (GLUergic) transmission, would protect central dopaminergic (DAergic) neurones from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the striatum in mice. MPTP decreased DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Riluzole protected against the MPTP-induced decrease in DA levels. The utilization of DA ([DOPAC+HVA]/DA) was increased after MPTP treatment, but returned to control values in mice given riluzole in combination with MPTP. Riluzole did not confer protection by inhibiting either monoamine oxidase type B activity or DA uptake. Possible mechanisms involved in the protective action of riluzole are discussed. Our results show that riluzole antagonizes the DAergic neurotoxicity of MPTP, a pro-parkinsonian neurotoxin, in mice.
我们研究了利鲁唑（一种干扰谷氨酸能传递的化合物）是否能保护中枢多巴胺能神经元免受1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠纹状体毒性。MPTP降低了多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的水平。利鲁唑可防止MPTP诱导的DA水平降低。MPTP处理后，DA的利用率（[DOPAC + HVA]/DA）增加，但在给予利鲁唑与MPTP联合治疗的小鼠中恢复到对照值。利鲁唑并非通过抑制单胺氧化酶B型活性或DA摄取来发挥保护作用。文中讨论了利鲁唑保护作用可能涉及的机制。我们的结果表明，利鲁唑可拮抗MPTP（一种帕金森病前体神经毒素）对小鼠的多巴胺能神经毒性。
