Ares J J, Outt P E
Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA.
Curr Pharm Des. 1998 Feb;4(1):17-36.
Over 30 million people in the world take non-steroidal anti-inflammatory drugs (NSAID's). A large percentage of these individuals will develop gastric ulcers and related complications, a condition known as "NSAID gastropathy". NSAID gastropathy differs from classic peptic ulcer disease in many ways, and traditional peptic ulcer therapy is largely ineffective in preventing NSAID-induced gastropathy. The prostaglandin misoprostol has been shown to be effective and is approved for the prevention of NSAID gastropathy. However, misoprostol has side effects that limit its general use. For this reason, considerable effort throughout the 1990's has focused on the identification of new gastroprotective molecules. Some synthetic studies have been aimed at the preparation of new prostaglandins, prostacyclin mimetics, and thromboxane antagonists. New histamine H2 receptor antagonists have also been developed which, unlike cimetidine or ranitidine, now appear to couple true gastroprotective activity with antisecretory properties. One new H2 antagonist, ebrotidine, has shown clinical utility in preventing NSAID gastropathy. Many other types of structures (flavonoids, peptides, terpenoids, xanthines, others), as well as compounds displaying certain pharmacological actions (5-hydroxytryptamine receptor binding, adrenergic receptor binding, mast cell stabilization, others) have been linked in some way to gastroprotection. This article reviews many of these recent gastroprotection findings, with emphasis on those of potential use for prevention of NSAID gastropathy.
全球有超过3000万人服用非甾体抗炎药（NSAID）。这些人中很大一部分会患上胃溃疡及相关并发症，这种情况被称为“NSAID胃病”。NSAID胃病在很多方面与经典的消化性溃疡病不同，传统的消化性溃疡治疗方法在预防NSAID引起的胃病方面大多无效。前列腺素米索前列醇已被证明是有效的，并且被批准用于预防NSAID胃病。然而，米索前列醇有副作用，限制了它的广泛使用。因此，整个20世纪90年代，人们都在致力于寻找新的胃保护分子。一些合成研究旨在制备新的前列腺素、前列环素类似物和血栓素拮抗剂。还开发了新型组胺H2受体拮抗剂，与西咪替丁或雷尼替丁不同，这些拮抗剂现在似乎将真正的胃保护活性与抗分泌特性结合在一起。一种新型H2拮抗剂依溴替丁已显示出在预防NSAID胃病方面的临床效用。许多其他类型的结构（黄酮类化合物、肽类、萜类、黄嘌呤类等），以及具有某些药理作用的化合物（5-羟色胺受体结合、肾上腺素能受体结合、肥大细胞稳定等）在某种程度上都与胃保护有关。本文综述了许多近期的胃保护研究结果，重点是那些对预防NSAID胃病有潜在用途的研究结果。
