Doble A
Vitry-Alfortville Research Centre, Rhône-Poulenc Rorer SA, Vitry-sur-Seine, France.
Neurology. 1996 Dec;47(6 Suppl 4):S233-41. doi: 10.1212/wnl.47.6_suppl_4.233s.
The excitotoxic hypothesis of neurodegeneration has stimulated much interest in the possibility of using compounds that will block excitotoxic processes to treat neurologic disorders. Riluzole is a neuroprotective drug that blocks glutamatergic neurotransmission in the CNS. Riluzole inhibits the release of glutamic acid from cultured neurons, from brain slices, and from corticostriatal neurons in vivo. It is thought these effects may be partly due to inactivation of voltage-dependent sodium channels on glutamatergic nerve terminals, as well as activation of a G-protein-dependent signal transduction process. Riluzole also blocks some of the postsynaptic effects of glutamic acid by noncompetitive blockade of N-methyl-D-aspartate (NMDA) receptors. In vivo, riluzole has neuroprotective, anticonvulsant, and sedative properties. In a rodent model of transient global cerebral ischemia, a complete suppression of the ischemia-evoked surge in glutamic acid release has been observed. In vitro, riluzole protects cultured neurons from anoxic damage, from the toxic effects of glutamic-acid-uptake inhibitors, and from the toxic factor in the CSF of patients with amyotrophic lateral sclerosis.
神经变性的兴奋性毒性假说激发了人们对使用能够阻断兴奋性毒性过程的化合物来治疗神经系统疾病可能性的浓厚兴趣。利鲁唑是一种神经保护药物，可阻断中枢神经系统中的谷氨酸能神经传递。利鲁唑抑制培养的神经元、脑片以及体内皮质纹状体神经元释放谷氨酸。据认为，这些作用可能部分归因于谷氨酸能神经末梢上电压依赖性钠通道的失活，以及G蛋白依赖性信号转导过程的激活。利鲁唑还通过非竞争性阻断N-甲基-D-天冬氨酸（NMDA）受体来阻断谷氨酸的一些突触后效应。在体内，利鲁唑具有神经保护、抗惊厥和镇静特性。在短暂性全脑缺血的啮齿动物模型中，已观察到缺血诱发的谷氨酸释放激增被完全抑制。在体外，利鲁唑可保护培养的神经元免受缺氧损伤、谷氨酸摄取抑制剂的毒性作用以及肌萎缩侧索硬化症患者脑脊液中有毒因子的影响。
