Abstract
Inhibition of prostaglandin biosynthesis via inhibition of the fatty acid cyclooxygenase (COX) is the mechanism of action of non-steroidal antiinflammatory drugs (NSAIDs). This results in an inhibition of the inflammatory and pain-producing activities of prostaglandins at a site of tissue injury but also in inhibition of prostaglandin production in the gastrointestinal tract (GI) and platelets, i.e. sites where endogenous prostaglandins are possibly involved in control of physiological functions. The discovery of two COX isoenzymes, COX-1 and COX-2, and the detection of their separate function and regulation, has initiated the search for new and putatively more selective inhibitors of prostaglandin biosynthesis. Specifically, selective inhibitors of COX-2 were developed in order to improve the anti-inflammatory and analgetic specificity and potency of the compounds and to reduce side-effects in the GI tract. Available experimental and clinical data of selective COX-2 inhibitors, including flosulide, celecoxib or rofecoxib, suggest improved gastric tolerance as compared to conventional, non-selective NSAIDs. However, experimental evidence suggests that both, the analgetic and anti-inflammatory action of COXinhibitors, might also require inhibition of COX-1. COX-2-selective compounds at antiinflammatory doses might have other side-effects, and for example reduce vascular prostacyclin production. Evidence is accumulating that COX-2 might not only be considered as a putatively detrimental enzyme but rather a highly regulated enzyme that also contributes to tissue protection and is even constitutively expressed in healthy human stomach mucosa. This paper reviews some of these newer aspects of COX-2-selective inhibitors in clinical use and discusses their possible benefits and risks.
Current Medicinal Chemistry
Title: Cyclooxygenase-2 Inhibition and Side-effects of Non-steroidal Antiinflammatory Drugs in the Gastrointestinal Tract.
Volume: 7 Issue: 11
Author(s): J. Meyer-Kirchrath and K. Schror
Affiliation:
Abstract: Inhibition of prostaglandin biosynthesis via inhibition of the fatty acid cyclooxygenase (COX) is the mechanism of action of non-steroidal antiinflammatory drugs (NSAIDs). This results in an inhibition of the inflammatory and pain-producing activities of prostaglandins at a site of tissue injury but also in inhibition of prostaglandin production in the gastrointestinal tract (GI) and platelets, i.e. sites where endogenous prostaglandins are possibly involved in control of physiological functions. The discovery of two COX isoenzymes, COX-1 and COX-2, and the detection of their separate function and regulation, has initiated the search for new and putatively more selective inhibitors of prostaglandin biosynthesis. Specifically, selective inhibitors of COX-2 were developed in order to improve the anti-inflammatory and analgetic specificity and potency of the compounds and to reduce side-effects in the GI tract. Available experimental and clinical data of selective COX-2 inhibitors, including flosulide, celecoxib or rofecoxib, suggest improved gastric tolerance as compared to conventional, non-selective NSAIDs. However, experimental evidence suggests that both, the analgetic and anti-inflammatory action of COXinhibitors, might also require inhibition of COX-1. COX-2-selective compounds at antiinflammatory doses might have other side-effects, and for example reduce vascular prostacyclin production. Evidence is accumulating that COX-2 might not only be considered as a putatively detrimental enzyme but rather a highly regulated enzyme that also contributes to tissue protection and is even constitutively expressed in healthy human stomach mucosa. This paper reviews some of these newer aspects of COX-2-selective inhibitors in clinical use and discusses their possible benefits and risks.
Export Options
About this article
Cite this article as:
Meyer-Kirchrath J. and Schror K., Cyclooxygenase-2 Inhibition and Side-effects of Non-steroidal Antiinflammatory Drugs in the Gastrointestinal Tract., Current Medicinal Chemistry 2000; 7 (11) . https://dx.doi.org/10.2174/0929867003374219
DOI https://dx.doi.org/10.2174/0929867003374219 |
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
-
<i>Salvia aucheri</i> Exhibits Antihypertensive Activity in Hypertensive Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry Psychoemotional Background of Temporomandibular Joint Dysfunction and Possible Drug Therapy
Letters in Drug Design & Discovery Clinical Applicability of Conditioning Techniques in Ischemia-Reperfusion Injury: A Review of the Literature
Current Cardiology Reviews Adverse Reactions Induced by Minocycline: A Review of Literature
Current Drug Safety Coumarins as Promising Scaffold for the Treatment of Age-related Diseases – An Overview of the Last Five Years
Current Topics in Medicinal Chemistry Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside
Current Vascular Pharmacology Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design The Impact of Metabolic Disease Associated with Metabolic Syndrome on Human Pregnancy
Current Pharmaceutical Biotechnology Digital Ulcers in Systemic Sclerosis – Frequency, Subtype Distribution and Clinical Outcome
Current Rheumatology Reviews Flavaglines: Their Discovery from Plants Used in Traditional Chinese Medicine, Synthesis, and Drug Development Against Cancer and Immune Disorders
Current Chinese Chemistry Applications of FDG-PET/CT in Assessment of Vascular Infection and Inflammation
Current Molecular Imaging (Discontinued) Flavones as a Privileged Scaffold in Drug Discovery: Current Developments
Current Organic Synthesis Testosterone Supplementation on Sarcopenia Components in Chronic Patients: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design Effect of Dietary Education on Cardiovascular Risk Factors in Rheumatoid Arthritis Patients
Current Rheumatology Reviews Non-Vitamin K Oral Anticoagulants (NOACs) A Review of Clinical Management and Laboratory Issues
Current Vascular Pharmacology A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update
Current Medicinal Chemistry Antiviral Activity and Molecular Targets of Plant Natural Products Against Avian Influenza Virus
Current Organic Chemistry Progress in Development of Group A Streptococcus Vaccines
Current Pharmaceutical Biotechnology An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Group A ß-hemolytic Streptococcal Pharyngitis: An Updated Review
Current Pediatric Reviews