Ledro Cano D, Gómez Rodríguez B J, Torres Domínguez Y, Hergueta Delgado P, Herrerías Esteban J M, Herrerías Gutiérrez J M
Servicio de Aparato Digestivo, Area Hospitalaria "Virgen Macarena", Sevilla, España.
Rev Esp Enferm Dig. 1999 Apr;91(4):305-9.
The discovery of, at least, two isoforms of the enzyme cyclooxygenase, named by the numbers 1 and 2, has updated our knowledge about the NSAID. This has led investigators to reconsider what we can expect from this kind of drugs. The two isoforms share enzymatic and structural properties, although they are regulated differently, at molecular level and can be distinguished from their functions, although an overlap of roles between them do exist. The main goal of the development of highly selective inhibitors is to improve gastric tolerability. The classical NSAID inhibit preferentially the isoform 1 of the cyclooxygenase, in vitro, which appears to be dangerous, according to gastrointestinal safety profile. The new compounds with high selectivity for the isoform 2 of the cyclooxygenase could be better tolerated at gastrointestinal level. Meanwhile these compounds also could have a potential use in several diseases such as colorectal cancer and neurodegenerative processes. The potential occurrence of side effects, perhaps related with renal function, should be noted. Finally large controlled clinical trials are needed to estimate the therapeutic advantages which can be offered by the new highly selective NSAID, and the potential consequences which can result from the isoform 2 of the cyclooxygenase prolonged inhibition
至少两种环氧化酶同工型（分别命名为1型和2型）的发现，更新了我们对非甾体抗炎药的认识。这使得研究人员重新思考我们对这类药物的期望。这两种同工型具有共同的酶学和结构特性，尽管它们在分子水平上的调节方式不同，并且可以从其功能上加以区分，尽管它们之间确实存在作用重叠。开发高选择性抑制剂的主要目标是提高胃耐受性。经典的非甾体抗炎药在体外优先抑制环氧化酶的1型同工型，从胃肠道安全性来看，这似乎是危险的。对环氧化酶2型同工型具有高选择性的新化合物在胃肠道水平上可能具有更好的耐受性。同时，这些化合物在诸如结直肠癌和神经退行性过程等多种疾病中也可能具有潜在用途。应注意可能出现的副作用，或许与肾功能有关。最后，需要进行大规模的对照临床试验，以评估新型高选择性非甾体抗炎药所能提供的治疗优势，以及环氧化酶2型同工型长期抑制可能产生的潜在后果。
