Repurposing of modafinil as an anti-inflammatory drug: a systematic review of experimental studies

Previous studies suggested the anti-inflammatory properties of modafinil. This study aimed to review the current literature to provide a comprehensive insight into the anti-inflammatory uses of modafinil in experimental studies. We conducted a systematic search using Medline (via PubMed), Web of Science, Scopus, and Embase databases from their commencement until 10 October 2022. All original articles focusing on modafinil anti-inflammatory effects were included. Our initial search yielded 1398 articles. Fourteen publications were included in our systematic review. Recent studies attempted to provide evidence for repurposing modafinil for several diseases, including autoimmune encephalomyelitis, nonalcoholic liver disease, gastric mucosal injury, neuropathic pain, atherosclerosis, intestinal ischemia, pulmonary hypertension, pancreatitis, ischemic stroke, testicular torsion, and lithium-pilocarpine-induced status epilepticus. Current evidence supports that modafinil can modulate inflammation, suppress the immune response, and improve disease severity partly by inhibiting NF-κB, NOS, Kca3.1, Kca2.3, and COX-2. By reviewing recent findings from experimental studies, we discussed the beneficial effects of modafinil on several inflammatory diseases, with a particular focus on the underlying mechanisms.