Abstract
Ischaemic stroke of the brain accounts for about one third of all deaths in industrialized countries. Many of the patients who survive are severily impaired. Thus, there is an enormous need for pharmacotherapy for the treatment of ischaemic stroke. Why is such a treatment not available yet? Are the pathophysiological sequelae of brain ischaemia not well understood? Have there been no attempts for clinical development of neuroprotective drugs? Everyone who is engaged in stroke research knows that the opposite is true: The cellular processes occuring after brain ischaemia have been studied for a long time, and we have a thorough understanding of the cellular processes which are involved. Many compounds underwent clinical trials, but most of them failed. One hypothesis to explain this disappointing fact might be that the cellular consequences of stroke are manyfold, but that the clinically tested compounds were selective for only one molecular mechanism. The aim of this review is to give a summary of the pathophysiological mechanisms which occur during and after an ischaemic stroke, and to comment on the preclinical studies where multiple disease-related mechanisms were targeted pharmacologically. Moreover, a novel class of neuroprotective compounds, the oxadiazole derivatives, will be presented. Compounds of this chemical class target two key mechanisms which are important for the pathophysiology of stroke, namely voltage-gated sodium channels, as well as glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype.
Keywords: ampa receptor antagonists, ischaemicstroke, thrombolysis, anti-excitotoxic principles
Current Pharmaceutical Design
Title: AMPA Receptor Antagonists with Additional Mechanisms of Action: New Opportunities for Neuroprotective Drugs?
Volume: 8 Issue: 10
Author(s): Thomas Weiser
Affiliation:
Keywords: ampa receptor antagonists, ischaemicstroke, thrombolysis, anti-excitotoxic principles
Abstract: Ischaemic stroke of the brain accounts for about one third of all deaths in industrialized countries. Many of the patients who survive are severily impaired. Thus, there is an enormous need for pharmacotherapy for the treatment of ischaemic stroke. Why is such a treatment not available yet? Are the pathophysiological sequelae of brain ischaemia not well understood? Have there been no attempts for clinical development of neuroprotective drugs? Everyone who is engaged in stroke research knows that the opposite is true: The cellular processes occuring after brain ischaemia have been studied for a long time, and we have a thorough understanding of the cellular processes which are involved. Many compounds underwent clinical trials, but most of them failed. One hypothesis to explain this disappointing fact might be that the cellular consequences of stroke are manyfold, but that the clinically tested compounds were selective for only one molecular mechanism. The aim of this review is to give a summary of the pathophysiological mechanisms which occur during and after an ischaemic stroke, and to comment on the preclinical studies where multiple disease-related mechanisms were targeted pharmacologically. Moreover, a novel class of neuroprotective compounds, the oxadiazole derivatives, will be presented. Compounds of this chemical class target two key mechanisms which are important for the pathophysiology of stroke, namely voltage-gated sodium channels, as well as glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype.
Export Options
About this article
Cite this article as:
Weiser Thomas, AMPA Receptor Antagonists with Additional Mechanisms of Action: New Opportunities for Neuroprotective Drugs?, Current Pharmaceutical Design 2002; 8 (10) . https://dx.doi.org/10.2174/1381612024607135
DOI https://dx.doi.org/10.2174/1381612024607135 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Potential Mechanisms Involved in the Anticonvulsant Effect of Methanol Extract of <i>Pyrenancantha staudtii</i> in Mice
Central Nervous System Agents in Medicinal Chemistry Personalized Treatment of Obsessive-Compulsive Disorder: Radiology, EEG, Pharmacogenetics and Biochemistry
Current Pharmacogenomics and Personalized Medicine Pleiotropic, Cardioprotective Effects of Omega-3 Polyunsaturated Fatty Acids
Mini-Reviews in Medicinal Chemistry Pharmacological Innovations for Posttraumatic Stress Disorder and Medication- Enhanced Psychotherapy
Current Pharmaceutical Design Inhibition of Histone Deacetylases: A Pharmacological Approach to the Treatment of Non-Cancer Disorders
Current Topics in Medicinal Chemistry Diacylglycerol Kinases as Emerging Potential Drug Targets for a Variety of Diseases
Current Drug Targets ABC Transporters: Unvalidated Therapeutic Targets in Cancer and the CNS
Anti-Cancer Agents in Medicinal Chemistry Chemistry, Biological Properties and SAR Analysis of Quinoxalinones
Mini-Reviews in Medicinal Chemistry Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) CT-negative Subarachnoid Hemorrhage Caused by Telangiectasia: A Case Report
Current Medical Imaging Caring for Children with Medical Complexity: Definitions, Challenges and Solutions
Current Pediatric Reviews Psychiatric Disorders and TRP Channels: Focus on Psychotropic Drugs
Current Neuropharmacology The Role of Neuroimaging in Our Understanding of the Suicidal Brain
CNS & Neurological Disorders - Drug Targets Growing up with Midazolam in the Neonatal and Pediatric Intensive Care
Current Drug Metabolism Medical Treatment for Neurocysticercosis: Drugs, Indications and Perspectives
Current Topics in Medicinal Chemistry Importance of ABC Transporters in Drug Development
Current Pharmaceutical Design Liposomes as Versatile Platform for Cancer Theranostics: Therapy, Bio-imaging, and Toxicological Aspects
Current Pharmaceutical Design Next Generation Sequencing in the Management of Leptomeningeal Metastases of Non-Small Cell Lung Cancer: A Case Report and Literature Review
Recent Patents on Anti-Cancer Drug Discovery Serotonergic and Cholinergic Strategies as Potential Targets for the Treatment of Schizophrenia
Current Pharmaceutical Design Traumatic Brain Injury and Blood-Brain Barrier Cross-Talk
CNS & Neurological Disorders - Drug Targets