Andrei Corina, Șeremet Oana Cristina, Pușcașu Ciprian, Zanfirescu Anca
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Biomedicines. 2025 Jul 13;13(7):1709. doi: 10.3390/biomedicines13071709.
Diabetic neuropathy (DN) remains a major clinical burden, characterized by progressive sensory dysfunction, pain, and impaired quality of life. Despite the available symptomatic treatments, there is a pressing need for disease-modifying therapies. In recent years, preclinical research has highlighted the potential of repurposed pharmacological agents, originally developed for other indications, to target key mechanisms of DN. This narrative review examines the main pathophysiological pathways involved in DN, including metabolic imbalance, oxidative stress, neuroinflammation, ion channel dysfunction, and mitochondrial impairment. A wide array of repurposed drugs-including antidiabetics (metformin, empagliflozin, gliclazide, semaglutide, and pioglitazone), antihypertensives (amlodipine, telmisartan, aliskiren, and rilmenidine), lipid-lowering agents (atorvastatin and alirocumab), anticonvulsants (topiramate and retigabine), antioxidant and neuroprotective agents (melatonin), and muscarinic receptor antagonists (pirenzepine, oxybutynin, and atropine)-have shown promising results in rodent models, reducing neuropathic pain behaviors and modulating underlying disease mechanisms. By bridging basic mechanistic insights with pharmacological interventions, this review aims to support translational progress toward mechanism-based therapies for DN.
糖尿病神经病变（DN）仍然是一项重大的临床负担，其特征为进行性感觉功能障碍、疼痛及生活质量受损。尽管有可用的对症治疗方法，但迫切需要改善病情的疗法。近年来，临床前研究凸显了最初为其他适应症开发的药物重新用于靶向DN关键机制的潜力。本叙述性综述探讨了DN所涉及的主要病理生理途径，包括代谢失衡、氧化应激、神经炎症、离子通道功能障碍和线粒体损伤。大量重新利用的药物——包括抗糖尿病药物（二甲双胍、恩格列净、格列齐特、司美格鲁肽和吡格列酮）、抗高血压药物（氨氯地平、替米沙坦、阿利吉仑和利美尼定）、降脂药物（阿托伐他汀和阿利西尤单抗）、抗惊厥药物（托吡酯和瑞替加滨）、抗氧化和神经保护药物（褪黑素）以及毒蕈碱受体拮抗剂（哌仑西平、奥昔布宁和阿托品）——在啮齿动物模型中已显示出有前景的结果，可减轻神经病理性疼痛行为并调节潜在的疾病机制。通过将基本的机制见解与药物干预相结合，本综述旨在支持向基于机制的DN治疗方法的转化进展。
