Abstract
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most widely prescribed or dispensed over the counter analgesics and antipyretics that act by inhibiting prostaglandins and thromboxane synthesis. After the identification of a second isoform of COX, the pharmaceutical research focused on developing COX-2- selective drugs (COXIBs) considered as second generation NSAIDs that would retain the anti-inflammatory and analgesic activities of traditional NSAID without blunting the gastrointestinal cytoprotection sustained by COX1-derived products such as PGE2. However, while several clinical trials confirmed a gastrointestinal safer profile of COXIBs vs unselective COX inhibitors, increasing evidence for potential cardiovascular risk associated with COXIBs rapidly emerged. Today, there are no really safe NSAIDs to be used in chronic pain and anti-inflammatory treatments, as an adequate therapy associated with a minimal gastrointestinal damage and cardiovascular toxicity is yet to be developed.
Objective: Here, we present evidences that combining the anti-aggregating and antiatherotrombotic activities of a thromboxane receptor antagonist with the antiinflammatory activity of a COXIB we could obtain a new multitarget drug providing protection against the harmful activities mediated by the COXIB component, yet exploiting its recognized therapeutic advantages as a gastrointestinal-safer anti-inflammatory drug. We also summarize recent progress achieved in this field of research and possible new strategies to obtain a new bivalent compound.
Conclusion: This possible third-generation NSAID with a safer pharmacological profile, will have all the pharmacological characteristics for the long-term therapy of chronic disorders such as inflammatory diseases or selected forms of cancer.
Keywords: Arachidonic acid, cardiovascular risk, COX-2 selective inhibitor, multitarget drug, non steroidal antiinflammatory drug, thromboxane receptor antagonist.
Current Medicinal Chemistry
Title:Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk
Volume: 24 Issue: 30
Author(s): Silvia Carnevali, Carola Buccellati , Chiara Bolego , Massimo Bertinaria , G. Enrico Rovati *Angelo Sala
Affiliation:
- Laboratory of Molecular and Eicosanoid Pharmacology, Dept. of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133 Milan,Italy
Keywords: Arachidonic acid, cardiovascular risk, COX-2 selective inhibitor, multitarget drug, non steroidal antiinflammatory drug, thromboxane receptor antagonist.
Abstract: Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most widely prescribed or dispensed over the counter analgesics and antipyretics that act by inhibiting prostaglandins and thromboxane synthesis. After the identification of a second isoform of COX, the pharmaceutical research focused on developing COX-2- selective drugs (COXIBs) considered as second generation NSAIDs that would retain the anti-inflammatory and analgesic activities of traditional NSAID without blunting the gastrointestinal cytoprotection sustained by COX1-derived products such as PGE2. However, while several clinical trials confirmed a gastrointestinal safer profile of COXIBs vs unselective COX inhibitors, increasing evidence for potential cardiovascular risk associated with COXIBs rapidly emerged. Today, there are no really safe NSAIDs to be used in chronic pain and anti-inflammatory treatments, as an adequate therapy associated with a minimal gastrointestinal damage and cardiovascular toxicity is yet to be developed.
Objective: Here, we present evidences that combining the anti-aggregating and antiatherotrombotic activities of a thromboxane receptor antagonist with the antiinflammatory activity of a COXIB we could obtain a new multitarget drug providing protection against the harmful activities mediated by the COXIB component, yet exploiting its recognized therapeutic advantages as a gastrointestinal-safer anti-inflammatory drug. We also summarize recent progress achieved in this field of research and possible new strategies to obtain a new bivalent compound.
Conclusion: This possible third-generation NSAID with a safer pharmacological profile, will have all the pharmacological characteristics for the long-term therapy of chronic disorders such as inflammatory diseases or selected forms of cancer.
Export Options
About this article
Cite this article as:
Carnevali Silvia , Buccellati Carola , Bolego Chiara, Bertinaria Massimo , Rovati Enrico G.*, Sala Angelo, Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk, Current Medicinal Chemistry 2017; 24 (30) . https://dx.doi.org/10.2174/0929867324666170602083428
DOI https://dx.doi.org/10.2174/0929867324666170602083428 |
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
-
Perspectives on Chemopreventive and Therapeutic Potential of Curcumin Analogs in Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Age-Related Sleep Disruption and Reduction in the Circadian Rhythm of Urine Output: Contribution to Nocturia?
Current Aging Science Therapeutic Potential for Thyroid Hormone Receptor-β Selective Agonists for Treating Obesity, Hyperlipidemia and Diabetes
Current Vascular Pharmacology Application of Stem Cells in Cardiology: Where we are and where we are Going
Current Stem Cell Research & Therapy Emerging Anti-inflammatory Therapies for Atherosclerosis
Current Pharmaceutical Design Synthesis of New 1-Substituted-1H-1,2,3,4-Tetrazoles from L-α-Amino Acids and Their Biological Assays
Letters in Organic Chemistry Antimicrobial Stewardship in the Neonatal Intensive Care Unit: An Update
Current Pediatric Reviews The Role of Mediterranean Diet, CoQ10 and Conjugated-Melatonin in Osteoporosis Primary Prevention and Therapy
Current Nutrition & Food Science New Frontiers in Regenerative Medicine in Cardiology: The Potential of Wharton’s Jelly Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Potential Benefits and Limits of Psychopharmacological Therapies in Pervasive Developmental Disorders
Current Clinical Pharmacology Incretin-Based Therapies, Glucometabolic Health and Endovascular Inflammation
Current Pharmaceutical Design Rapid and Simple Profiling of Lipoproteins by Polyacrylamide-Gel Disc Electrophoresis to Determine the Heterogeneity of Low-Density Lipoproteins (LDLs) Including Small, Dense LDL
Recent Patents on Cardiovascular Drug Discovery Benefits of Exercise Training in Secondary Prevention of Coronary and Peripheral Arterial Disease
Vascular Disease Prevention (Discontinued) Living Heart Valve and Small-Diameter Artery Substitutes - An Emerging Field for Intellectual Property Development
Recent Patents on Biotechnology Severe Acute Respiratory Syndrome (SARS): A Brief Review With Exploration of the Outcomes, Prognostic Factors and Sequelae
Current Respiratory Medicine Reviews ATP Binding Cassette Transporter A1 (ABCA1) Associated Proteins:Potential Drug Targets in the Metabolic Syndrome and Atherosclerotic Disease?
Current Pharmaceutical Biotechnology A Systematic Review of Overweight, Obesity, and Type 2 Diabetes Among Asian American Subgroups
Current Diabetes Reviews Association between Antiretroviral Treatment and Markers of Systemic Inflammation among HIV Patients in Ghana
Current HIV Research The Roles of MicroRNAs in Heart Diseases: A Novel Important Regulator
Current Medicinal Chemistry Antithrombotic Therapy After TAVR
Current Vascular Pharmacology