Neuroprotective effects of riluzole in Alzheimer's disease: A comprehensive review

• Published in: Fundamental & clinical pharmacology 2024-04, Vol.38 (2), p.225-237
• Main Authors: Golmohammadi, Maryam, Mahmoudian, Mohammadreza, Hasan, Ekhlas Khammas, Alshahrani, Shadia Hamoud, Romero‐Parra, Rosario Mireya, Malviya, Jitendra, Hjazi, Ahmed, Najm, Mazin A. A., Almulla, Abbas F., Zamanian, Mohammad Yasin, Kadkhodaei, Mona, Mousavi, Nazanin
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; amyloid beta; Calcium; Calcium channels; Calcium channels (voltage-gated); Clinical trials; Disease; Drug development; Drugs; Erythropoietin; Excitatory amino acid transporters; Excitotoxicity; Glutamic acid; Glutamic acid receptors (ionotropic); Lithium; Medical treatment; Memantine; Minocycline; Molecular modelling; N-Methyl-D-aspartic acid receptors; Neurodegenerative diseases; Neuroprotection; Patients; Piracetam; riluzole; Search engines; Silymarin; Sodium; Sodium channels (voltage-gated); α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12955

Background Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. Objective The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. Methods The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. Results Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage‐dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1‐EAAT2. Conclusion In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease.