Abstract
Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease of the human motor system. Aetiological mechanisms implicated in the development of ALS have been linked to the glutamatergic neurotransmitter system, with destruction of motor neurons triggered through excessive activation of glutamate receptors at the synaptic cleft. This ‘excitotoxicity’ theory of ALS gave rise to the development of therapeutic approaches and ultimately clinical trials involving riluzole, initially thought to act solely as an inhibitor of glutamate release. Subsequent effects of riluzole have been postulated to include indirect antagonism of glutamate receptors, in addition to inactivation of neuronal voltage-gated Na+ channels. Riluzole remains the only disease-modifying therapy available to patients with ALS. Despite having been clinically available since the mid-1990s, the in vivo pharmacological targets of riluzole have been poorly defined. An improved understanding concerning the potential neuroprotective mechanisms of riluzole may unearth pathophysiological processes that mediate neurodegeneration in ALS. The present review summarises the known chemical and pharmacological properties of riluzole. The failure of other putative neuroprotective therapies to demonstrate positive treatment outcomes in this intractable disease will be reviewed. Finally, the hypothesis that Na+ conductances may be involved in the processes of neuronal and axonal degeneration in ALS will be explored.
Keywords: Amyotrophic lateral sclerosis, motor neuron disease, motor neuron, clinical trial, glutamate, excitotoxicity, riluzole
Current Medicinal Chemistry
Title: Riluzole, Neuroprotection and Amyotrophic Lateral Sclerosis
Volume: 17 Issue: 18
Author(s): B.C. Cheah, S. Vucic, A. V. Krishnan and M.C. Kiernan
Affiliation:
Keywords: Amyotrophic lateral sclerosis, motor neuron disease, motor neuron, clinical trial, glutamate, excitotoxicity, riluzole
Abstract: Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease of the human motor system. Aetiological mechanisms implicated in the development of ALS have been linked to the glutamatergic neurotransmitter system, with destruction of motor neurons triggered through excessive activation of glutamate receptors at the synaptic cleft. This ‘excitotoxicity’ theory of ALS gave rise to the development of therapeutic approaches and ultimately clinical trials involving riluzole, initially thought to act solely as an inhibitor of glutamate release. Subsequent effects of riluzole have been postulated to include indirect antagonism of glutamate receptors, in addition to inactivation of neuronal voltage-gated Na+ channels. Riluzole remains the only disease-modifying therapy available to patients with ALS. Despite having been clinically available since the mid-1990s, the in vivo pharmacological targets of riluzole have been poorly defined. An improved understanding concerning the potential neuroprotective mechanisms of riluzole may unearth pathophysiological processes that mediate neurodegeneration in ALS. The present review summarises the known chemical and pharmacological properties of riluzole. The failure of other putative neuroprotective therapies to demonstrate positive treatment outcomes in this intractable disease will be reviewed. Finally, the hypothesis that Na+ conductances may be involved in the processes of neuronal and axonal degeneration in ALS will be explored.
Export Options
About this article
Cite this article as:
Cheah B.C., Vucic S., Krishnan V. A. and Kiernan M.C., Riluzole, Neuroprotection and Amyotrophic Lateral Sclerosis, Current Medicinal Chemistry 2010; 17 (18) . https://dx.doi.org/10.2174/092986710791163939
DOI https://dx.doi.org/10.2174/092986710791163939 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Drug Screening for Huntingtons Disease and other Neurodegenerative Disorders
Current Molecular Pharmacology Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication
Anti-Cancer Agents in Medicinal Chemistry Stem Cells and Translational Medicine: From Research to Clinical Procedures
Current Tissue Engineering (Discontinued) Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Inhibitors of Nitric Oxide Synthase: What's up and What's Next?
Current Enzyme Inhibition Application of Polymeric Nanoparticles for CNS Targeted Zinc Delivery In Vivo
CNS & Neurological Disorders - Drug Targets Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Protein Chemistry of Amyloid Fibrils and Chaperones: Implications for Amyloid Formation and Disease
Current Chemical Biology Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study
Current Alzheimer Research Editorial [Hot Topic: The Pineal Hormone Melatonin in Health and Disease (Guest Editors: Charanjit Kaur)]
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Promotion of Apoptosis in Cancer Cells by Selective Purine-Derived Pharmacological CDK Inhibitors: One Outcome, Many Mechanisms
Current Pharmaceutical Design Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters Therapeutic Nucleic Acids
Recent Patents on Regenerative Medicine Preface
Current Enzyme Inhibition Crystal Structure of a Cu,Zn Superoxide Dismutase From the Thermophilic Fungus <i>Chaetomium thermophilum</i>
Protein & Peptide Letters Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications
Current Medicinal Chemistry Development of Neurotrophic Molecules for Treatment of Neurode-generation
Current Protein & Peptide Science Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design Editorial [Hot Topic: Emerging Roles of the Unfolded Protein Response Signaling in Physiology and Disease (Executive Editor: Claudio A. Hetz and Claudio Soto )]
Current Molecular Medicine Snake Venom: From Deadly Toxins to Life-saving Therapeutics
Current Medicinal Chemistry