Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk

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.

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