Department of Biochemistry & Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Neuroscientist. 2021 Dec;27(6):620-649. doi: 10.1177/1073858420961078. Epub 2020 Oct 22.
Traumatic brain injury (TBI) remains a significant leading cause of death and disability among adults and children globally. To date, there are no Food and Drug Administration-approved drugs that can substantially attenuate the sequelae of TBI. The innumerable challenges faced by the conventional de novo discovery of new pharmacological agents led to the emergence of alternative paradigm, which is drug repurposing. Repurposing of existing drugs with well-characterized mechanisms of action and human safety profiles is believed to be a promising strategy for novel drug use. Compared to the conventional discovery pathways, drug repurposing is less costly, relatively rapid, and poses minimal risk of the adverse outcomes to study on participants. In recent years, drug repurposing has covered a wide range of neurodegenerative diseases and neurological disorders including brain injury. This review highlights the advances in drug repurposing and presents some of the promising candidate drugs for potential TBI treatment along with their possible mechanisms of neuroprotection. Edaravone, glyburide, ceftriaxone, levetiracetam, and progesterone have been selected due to their potential role as putative TBI neurotherapeutic agents. These drugs are Food and Drug Administration-approved for purposes other than brain injuries; however, preclinical and clinical studies have shown their efficacy in ameliorating the various detrimental outcomes of TBI.
创伤性脑损伤（TBI）仍然是全球成年人和儿童死亡和残疾的主要原因。迄今为止，尚无美国食品和药物管理局批准的药物可以显著减轻 TBI 的后遗症。由于传统的从头发现新的药理制剂面临无数挑战，因此出现了替代范式，即药物再利用。具有明确作用机制和人类安全概况的现有药物的再利用被认为是一种有前途的新药使用策略。与传统的发现途径相比，药物再利用成本更低、相对较快，并且对参与者的研究产生不良后果的风险最小。近年来，药物再利用涵盖了广泛的神经退行性疾病和神经系统疾病，包括脑损伤。本综述重点介绍了药物再利用的进展，并介绍了一些有希望的候选药物，用于潜在的 TBI 治疗及其可能的神经保护机制。依达拉奉、格列本脲、头孢曲松、左乙拉西坦和孕酮因其可能作为 TBI 神经治疗剂的作用而被选中。这些药物已获得美国食品和药物管理局批准用于治疗脑损伤以外的疾病；然而，临床前和临床研究表明它们在改善 TBI 的各种不良后果方面具有疗效。
