Abstract
Following the discovery of inducible COX-2 in arthritic joint fluid and immunocompetent cells a revolution in the field of antiinflammatory treatment was expected. The detection of a constitutive COX-2 in the kidney, in stomach and central nervous system destroyed this hypotheses. Further experiments in animal models were done to elucidate the role of the constitutive COX-2 in different physiological and pathophysiological states. In central nervous system was shown that the constitutive COX-2 is the predominant isoform of cyclooxygenases in brain and spinal cord and is highly regulated by different mediators. After experimental induction of peripheral inflammation a significant induction of COX-2 gene, protein expression and synthesis of prostaglandins in the spinal cord was detected. It was concluded that COX-2 is strongly involved in pain mediation processing in the spinal cord. The detection of COX-2 in the brain endothelial cells and its role in fever led to new insights of development and time course of temperature elevation. Probably, the use of selective COX-2 inhibitors decreases fever more effective than “classical” antipyretics. Furthermore, newer results show a role of COX-2 in differentiation and maturation processes in brain. These findings implicate new ways for the treatment of Alzheimers disease and other degenerative brain disorders. Clinical and experimental results with selective COX-2 inhibitors show a better safety profile than non-selective COX inhibitors. The clinical use after drug registration will be decide on the further role of this new class of drugs in analgesic/antiinflammatory therapy and on new fields of clinical use.
Current Medicinal Chemistry
Title: COX-2 in Brain and Spinal Cord - Implications for Therapeutic Use.
Volume: 7 Issue: 11
Author(s): C. Hoffmann
Affiliation:
Abstract: Following the discovery of inducible COX-2 in arthritic joint fluid and immunocompetent cells a revolution in the field of antiinflammatory treatment was expected. The detection of a constitutive COX-2 in the kidney, in stomach and central nervous system destroyed this hypotheses. Further experiments in animal models were done to elucidate the role of the constitutive COX-2 in different physiological and pathophysiological states. In central nervous system was shown that the constitutive COX-2 is the predominant isoform of cyclooxygenases in brain and spinal cord and is highly regulated by different mediators. After experimental induction of peripheral inflammation a significant induction of COX-2 gene, protein expression and synthesis of prostaglandins in the spinal cord was detected. It was concluded that COX-2 is strongly involved in pain mediation processing in the spinal cord. The detection of COX-2 in the brain endothelial cells and its role in fever led to new insights of development and time course of temperature elevation. Probably, the use of selective COX-2 inhibitors decreases fever more effective than “classical” antipyretics. Furthermore, newer results show a role of COX-2 in differentiation and maturation processes in brain. These findings implicate new ways for the treatment of Alzheimers disease and other degenerative brain disorders. Clinical and experimental results with selective COX-2 inhibitors show a better safety profile than non-selective COX inhibitors. The clinical use after drug registration will be decide on the further role of this new class of drugs in analgesic/antiinflammatory therapy and on new fields of clinical use.
Export Options
About this article
Cite this article as:
Hoffmann C., COX-2 in Brain and Spinal Cord - Implications for Therapeutic Use., Current Medicinal Chemistry 2000; 7 (11) . https://dx.doi.org/10.2174/0929867003374282
DOI https://dx.doi.org/10.2174/0929867003374282 |
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
-
Looking for Organ Damages Due to Anabolic-androgenic Steroids (AAS): Is Oxidative Stress the Culprit?
Mini-Reviews in Organic Chemistry Is Ecto-nucleoside Triphosphate Diphosphohydrolase (NTPDase)-based Therapy of Central Nervous System Disorders Possible?
Mini-Reviews in Medicinal Chemistry PPARs as Drug Targets to Modulate Inflammatory Responses?
Current Drug Targets - Inflammation & Allergy P2X7 Receptor-Associated Programmed Cell Death in the Pathophysiology of Hemorrhagic Stroke
Current Neuropharmacology Renin Angiotensin System as a Regulator of Cell Volume. Implications to Myocardial Ischemia
Current Cardiology Reviews Can microRNAs be Biomarkers or Targets for Therapy of Ischemic Coronary Artery Disease in Metabolic Syndrome?
Current Drug Targets Acellular Spinal Cord Scaffold Implantation Promotes Vascular Remodeling with Sustained Delivery of VEGF in a Rat Spinal Cord Hemisection Model
Current Neurovascular Research Sirolimus Early Graft Nephrotoxicity: Clinical and Experimental Data
Current Drug Safety Cardioprotection with opioids - Trusted old friends -Clinical Science -
Current Pharmaceutical Design Exploration of the Medicinal Peptide Space
Protein & Peptide Letters P-Selectin Antagonism in Inflammatory Disease
Current Pharmaceutical Design In Vivo Imaging of the Diseased Nervous System: An Update
Current Pharmaceutical Design Models for the Study of Angiogenesis
Current Pharmaceutical Design Mechanism-Based Inhibitors from Phytomedicine: Risks of Hepatotoxicity and their Potential Hepatotoxic Substructures
Current Drug Metabolism Endoplasmic Reticulum Dysfunction in Brain Pathology: Critical Role of Protein Synthesis
Current Neurovascular Research A Quantitative Proteomic Analysis to Reveal Effects of N-acetylcysteine on H<sub>2</sub>O<sub>2</sub>-induced Cytotoxicity
Current Proteomics Coumarin and Isocoumarin as Serine Protease Inhibitors
Current Pharmaceutical Design Soluble Epoxide Hydrolase, a Target with Multiple Opportunities for Cardiovascular Drug Discovery
Current Topics in Medicinal Chemistry Tetrahydrobiopterin: A Vascular Redox Target to Improve Endothelial Function
Current Vascular Pharmacology Autophagy Inhibition Rescues Against Leptin-Induced Cardiac Contractile Dysfunction
Current Pharmaceutical Design