摘要
背景: 非甾体抗炎药(NSAIDs)是通过抑制前列腺素和血栓素合成起作用的逆止痛剂和解热药物中最广泛处方或分配的一些。在鉴定COX的第二同种型后,药物研究集中在开发被认为是第二代NSAID的COX-2-选择性药物(COXIBs),其将保留传统NSAID的抗炎和止痛活性,而不会使胃肠道细胞保护受损COX1衍生产品如PGE2。然而,虽然几项临床试验证实了COXIBs与非选择性COX抑制剂的胃肠道更安全的特征,但与COXIB相关的潜在心血管风险的越来越多的证据迅速出现。今天,没有真正安全的NSAID可用于慢性疼痛和抗炎治疗,因为与最小的胃肠道损伤和心血管毒性有关的适当治疗尚待开发。 目的:在这里,我们提出结合血栓素受体拮抗剂的抗凝集和抗血栓形成活性与COXIB的抗炎活性结合的证据,我们可以获得一种新的多靶点药物,提供针对COXIB组分介导的有害活性的保护,但利用其公认的治疗优势作为胃肠道更安全的抗炎药物。我们还总结了近期在这一研究领域取得的进展和可能的新策略,以获得新的二价化合物。 结论:这种具有更安全药理学特征的这种可能的第三代NSAID将具有长期治疗慢性疾病如炎性疾病或选定形式癌症的所有药理学特征。
关键词: 花生四烯酸,心血管风险,COX-2选择性抑制剂,多靶药物,非甾体抗炎药,血栓素受体拮抗剂。
Current Medicinal Chemistry
Title:Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk
Volume: 24 Issue: 30
关键词: 花生四烯酸,心血管风险,COX-2选择性抑制剂,多靶药物,非甾体抗炎药,血栓素受体拮抗剂。
摘要: 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.
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Cite this article as:
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 |
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