The pharmacology and mechanism of action of riluzole
The pharmacology and mechanism of action of riluzole
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DOI：
10.1212/wnl.47.6_suppl_4.233s
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发表时间：
1996-12-01
期刊：
影响因子：
9.9
通讯作者：
Doble, A
中科院分区：
文献类型：
--
作者：
Doble, A
神经变性的兴奋性毒性假说激发了人们对使用将阻断的化合物的可能性的兴趣。兴奋性毒性过程来治疗神经系统疾病。阿曲唑是一种神经保护药物，可阻断CNS中的多巴胺能神经传递。阿曲唑抑制谷氨酸从培养的神经元、脑切片和体内皮质纹状体神经元的释放。据认为，这些影响可能部分是由于在多巴胺能神经末梢上的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。阿曲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、抗惊厥和镇静作用。在短暂性全脑缺血的啮齿动物模型中，已经观察到对缺血诱发的谷氨酸释放激增的完全抑制。在体外，利鲁唑保护培养的神经元免受缺氧损伤，免受谷氨酸摄取抑制剂的毒性作用，以及免受肌萎缩侧索硬化症患者CSF中的毒性因子的影响。
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.