Yimer Ebrahim M, Hishe Hailemichael Zeru, Tuem Kald Beshir
Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.
Front Neurosci. 2019 Mar 26;13:236. doi: 10.3389/fnins.2019.00236. eCollection 2019.
To date, there is no cure or disease-modifying agents available for most well-known neurological disorders. Current therapy is typically focused on relieving symptoms and supportive care in improving the quality of life of affected patients. Furthermore, the traditional drug discovery technique is more challenging, particularly for neurological disorders. Therefore, the repurposing of existing drugs for these conditions is believed to be an efficient and dynamic approach that can substantially reduce the investments spent on drug development. Currently, there is emerging evidence that suggests the potential effect of a beta-lactam antibiotic, ceftriaxone (CEF), to alleviate the symptoms of different experimentally-induced neurological disorders: Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, epileptic-seizure, brain ischemia, traumatic brain injuries, and neuropathic pain. CEF also affects the markers of oxidative status and neuroinflammation, glutamatergic systems as well as various aggregated toxic proteins involved in the pathogenesis of different neurological disorders. Moreover, it was found that CEF administration to drug dependent animal models improved the withdrawal symptoms upon drug discontinuation. Thus, this review aimed to describe the effects of CEF against multiple models of neurological illnesses, drug dependency, and withdrawal. It also emphasizes the possible mechanisms of neuroprotective actions of CEF with respective neurological maladies.
迄今为止,对于大多数知名的神经疾病,尚无治愈方法或疾病修饰药物。当前的治疗通常侧重于缓解症状以及提供支持性护理以提高受影响患者的生活质量。此外,传统的药物发现技术更具挑战性,尤其是对于神经疾病而言。因此,将现有药物重新用于这些病症被认为是一种高效且动态的方法,可大幅减少药物开发的投入。目前,越来越多的证据表明,一种β-内酰胺抗生素头孢曲松(CEF)可能对缓解不同实验性诱导的神经疾病症状有效,这些疾病包括帕金森病、阿尔茨海默病、肌萎缩侧索硬化症、癫痫发作、脑缺血、创伤性脑损伤和神经性疼痛。CEF还会影响氧化状态和神经炎症的标志物、谷氨酸能系统以及参与不同神经疾病发病机制的各种聚集性毒性蛋白。此外,研究发现,对药物依赖动物模型给予CEF可改善停药后的戒断症状。因此,本综述旨在描述CEF对多种神经疾病、药物依赖和戒断模型的影响。它还强调了CEF针对相应神经疾病发挥神经保护作用的可能机制。