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
-
Subject Index To Volume 6
Current Molecular Medicine Cytopathological Mechanisms in Mitochondrial Disease
Current Chemical Biology Longevity Pathways: HSF1 and FoxO Pathways, a New Therapeutic Target to Prevent Age-Related Diseases
Current Aging Science The Multiple Layers of Signaling Selectivity at Protease-Activated Receptors
Current Pharmaceutical Design Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer's Disease
Current Pharmaceutical Design MicroRNAs: Macro Challenges on Understanding Human Biological Functions and Neurological Diseases
Current Molecular Medicine The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review
CNS & Neurological Disorders - Drug Targets Immunotherapeutic Approaches in MS: Update on Pathophysiology and Emerging Agents or Strategies 2006
Endocrine, Metabolic & Immune Disorders - Drug Targets Beneficial Effects of Dietary Supplements Against Mitochondrial Dysfunction and Apoptosis in Neurodegenerative Diseases
Current Pharmacogenomics and Personalized Medicine Anti-aging Natural Compounds and their Role in the Regulation of Metabolic Pathways Leading to Longevity
Mini-Reviews in Medicinal Chemistry Therapy for Dominant Inherited Diseases by Allele-Specific RNA Interference: Successes and Pitfalls
Current Gene Therapy Metabotropic Glutamate Receptors in the Control of Neuronal Activity and as Targets for Development of Anti-Epileptogenic Drugs
Current Medicinal Chemistry Assessing the Effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India
Current HIV Research Defective HIF Signaling Pathway and Brain Response to Hypoxia in Neurodegenerative Diseases: Not an “Iffy” Question!
Current Pharmaceutical Design S-Nitrosylation: Targets, Controls and Outcomes
Current Genomics Promotion of Apoptosis in Cancer Cells by Selective Purine-Derived Pharmacological CDK Inhibitors: One Outcome, Many Mechanisms
Current Pharmaceutical Design Strategies for Skeletal Muscle Targeting in Drug Discovery
Current Pharmaceutical Design The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology Special Issue on Stem Cells: An Introduction from the Guest Editor
Current Neurovascular Research Editorial [Hot Topic: Mitochondria as a Pharmacological Target: A Clue for Efficacy and a Reason for Toxicity (Executive Guest Editor: Nadezda Apostolova)]
Current Pharmaceutical Design