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
-
Selenium and Clinical Trials: New Therapeutic Evidence for Multiple Diseases
Current Medicinal Chemistry Mesenchymal Stromal Cells from Umbilical Cord Blood
Current Stem Cell Research & Therapy Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases
Current Alzheimer Research ER Stress and UPR in Familial Amyotrophic Lateral Sclerosis
Current Molecular Medicine Vascular Endothelial Growth Factor: Adaptive Changes in the Neuroglialvascular Unit
Current Neurovascular Research Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases
CNS & Neurological Disorders - Drug Targets 5-Adenosine Monophosphate-Activated Protein Kinase and the Metabolic Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Roles of p75NTR in Maintaining Brain Hemostasis and the Implications for p75NTR-targeted Therapies
Current Alzheimer Research SOD1 Aggregation and ALS: Role of Metallation States and Disulfide Status
Current Topics in Medicinal Chemistry Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Tackling Chronic Pain and Inflammation through the Purinergic System
Current Medicinal Chemistry Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases
Current Medicinal Chemistry Pharmaceutical Targeting of the Brain
Current Pharmaceutical Design microRNAs in Cardiovascular Disease: Small Molecules but Big Roles
Current Topics in Medicinal Chemistry Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition
Current Medicinal Chemistry The Molecular Basis of Conantokin Antagonism of NMDA Receptor Function
Current Drug Targets Therapeutic Potential of Cannabinoids in the Treatment of Neuroinflammation Associated with Parkinsons Disease
Mini-Reviews in Medicinal Chemistry Ultra-micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Defining the Mechanism of Action of 4-Phenylbutyrate to Develop a Small-Molecule-Based Therapy for Alzheimers Disease
Current Medicinal Chemistry Role of Prostaglandins in Multiple Sclerosis
Current Pharmaceutical Design