Patrono Carlo, Rocca Bianca
Department of Pharmacology, Catholic University School of Medicine, Rome, Italy.
Pharmacol Res. 2009 May;59(5):285-9. doi: 10.1016/j.phrs.2009.01.011. Epub 2009 Feb 5.
Currently available NSAIDs represent a heterogeneous group of therapeutic agents characterized by a variable benefit/risk profile. The development of a new class of selective COX-2 inhibitors, the coxibs, has contributed importantly to clarifying the discrete roles of COX-2 vs. COX-1 inhibition in different aspects of NSAID-related efficacy and safety. Cardiovascular toxicity has emerged as a previously unrecognized, mechanism-based effect of COX-2 inhibitors. Lessons learned from the many facets of the coxib failure story may help guiding the successful development of a new class of safer NSAIDs, targeting mediators unrelated to arachidonic acid metabolism or molecular targets downstream of COX-isozymes.
目前可用的非甾体抗炎药（NSAIDs）是一类异质性治疗药物，其效益/风险状况各不相同。新型选择性环氧化酶-2（COX-2）抑制剂（即昔布类药物）的研发，对阐明COX-2与COX-1抑制在NSAIDs相关疗效和安全性不同方面的各自作用做出了重要贡献。心血管毒性已成为COX-2抑制剂一种此前未被认识的、基于机制的效应。从昔布类药物失败事件的诸多方面吸取的教训，可能有助于指导研发一类新型更安全的NSAIDs，这类药物以与花生四烯酸代谢无关的介质或COX同工酶下游的分子靶点为作用对象。
