Department of Surgery, Division of Neurosurgery and Spinal Program, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.
J Neurosurg Spine. 2012 Sep;17(1 Suppl):151-6. doi: 10.3171/2012.4.AOSPINE1259.
In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889.
在创伤性脊髓损伤（SCI）后即刻，多种继发性损伤机制共同作用，逐渐扩大初始损伤部位，可能导致长期随访时神经功能恢复不佳。利鲁唑是一种苯并噻唑类药物，基于钠通道阻断和减轻谷氨酸毒性具有神经保护作用，目前是一种已批准的药物，可减轻肌萎缩侧索硬化症患者的神经元变性程度。此外，几项 SCI 的临床前研究表明，利鲁唑的给药与改善的功能结果和增加的神经组织保存有关。基于这些发现，利鲁唑作为治疗 SCI 的潜在神经保护药物引起了相当大的关注。目前，北美临床试验网络（NACTN）正在进行一项评估利鲁唑在人类 SCI 患者中的安全性和药代动力学特征的 I 期临床试验，用于治疗脊髓损伤。本综述总结了利鲁唑现有的临床前和临床文献，详细描述了 I 期试验，并提出了未来研究的潜在机会。临床试验注册号：NCT00876889。
