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
-
Bone Marrow Cell Therapy in Clinical Trials: A Review of the Literature
Reviews on Recent Clinical Trials Immunosuppression in Sepsis
Current Pharmaceutical Design Synthesis and Evaluation of 1-hydroxybenzotriazole Derivatives: Dual Inhibitors of Carbonic Anhydrase II and Sodium Hydrogen Exchanger I
Letters in Organic Chemistry p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Heat Shock Proteins in Diabetes and Wound Healing
Current Protein & Peptide Science Synthesis and Evaluation of Indole Based Molecules for Treatment of Oxidative Stress Related Diseases
Current Topics in Medicinal Chemistry Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) The Role of Cytokines in Pharmacological Modulation of Hepatic Ischemia/Reperfusion Injury
Current Pharmaceutical Design Aldehyde Dehydrogenase-2 Roles in Ischemic Cardiovascular Disease
Current Drug Targets Oral Antiplatelet Therapy for Acute Coronary Syndromes: Aspirin, P2Y12 Inhibition and Thrombin Receptor Antagonists
Current Drug Targets Subject Index To Volume 6
Cardiovascular & Hematological Disorders-Drug Targets Natural Occurring Compounds Inhibit Osteoclastogenesis via Targeting NFATc1-related Signaling Pathways
Current Drug Targets Oxidative Stress and Drugs of Abuse: An Update
Mini-Reviews in Organic Chemistry The Role of Trimetazidine After Acute Myocardial Infarction
Current Vascular Pharmacology Potential Use of Vanadium Compounds in Therapeutics
Current Medicinal Chemistry Glycogen Synthase Kinase-3 Beta; A New Target in Pancreatic Cancer?
Current Cancer Drug Targets From Erythropoietin to Its Peptide Derivatives: Smaller but Stronger
Current Protein & Peptide Science Potential of Sulphur-containing Amino Acids in the Prevention of Catecholamine-induced Arrhythmias
Current Medicinal Chemistry Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes
Current Pharmaceutical Design Toll-Like Receptors and Kidney Diseases
Inflammation & Allergy - Drug Targets (Discontinued)