Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Opposite Air Force Station, Palaj, P.O-382355, Gandhinagar, Gujarat, India.
Pharmaceut Med. 2023 Nov;37(6):463-490. doi: 10.1007/s40290-023-00499-3. Epub 2023 Sep 12.
Spinal cord injury (SCI) encompasses a plethora of complex mechanisms like the involvement of major cell death pathways, neurodegeneration of spinal cord neurons, overexpression of glutaminergic transmission and inflammation cascade, along with different co-morbidities like neuropathic pain, urinary and sexual dysfunction, respiratory and cardiac failures, making it one of the leading causes of morbidity and mortality globally. Corticosteroids such as methylprednisolone and dexamethasone, and non-steroidal anti-inflammatory drugs such as naproxen, aspirin and ibuprofen are the first-line treatment options for SCI, inhibiting primary and secondary progression by preventing inflammation and action of reactive oxygen species. However, they are constrained by a short effective drug administration window and their pharmacological action being limited to symptomatic relief of the secondary effects related to spinal cord injury only. Although post-injury rehabilitation treatments may enable functional recovery, they take a long time to show results. Drug repurposing might be an innovative method for expanding therapy alternatives, utilising drugs that are already approved by various esteemed federal agencies throughout the world. Reutilising a drug molecule to treat SCI can eliminate the need for expensive and lengthy drug discovery processes and pave the way for new therapeutic approaches in SCI. This review summarises marketed drugs that could be repurposed based on their safety and efficacy data. We also discuss their mechanisms of action and provide a list of repurposed drugs under clinical trials for SCI therapy.
脊髓损伤(SCI)涉及多种复杂机制,如主要细胞死亡途径的参与、脊髓神经元的神经退行性变、谷氨酰胺能传递和炎症级联的过度表达,以及神经病理性疼痛、尿失禁和性功能障碍、呼吸和心脏衰竭等不同合并症,使其成为全球发病率和死亡率的主要原因之一。 甲泼尼龙和地塞米松等皮质类固醇和萘普生、阿司匹林和布洛芬等非甾体抗炎药是 SCI 的一线治疗选择,通过预防炎症和活性氧的作用来抑制原发性和继发性进展。 然而,它们受到有效药物治疗窗口短和其药理作用仅限于缓解与脊髓损伤相关的继发性影响的限制。 尽管受伤后的康复治疗可能使功能得到恢复,但需要很长时间才能显示出结果。 药物再利用可能是扩大治疗选择的一种创新方法,利用已经得到全球各种著名联邦机构批准的药物。 重新利用药物分子来治疗 SCI 可以消除昂贵和漫长的药物发现过程的需要,并为 SCI 治疗开辟新的治疗方法。 这篇综述总结了基于安全性和疗效数据可以重新利用的上市药物。 我们还讨论了它们的作用机制,并提供了一份正在进行临床试验用于 SCI 治疗的重新利用药物清单。