Tabuchi Y, Kurebayashi Y
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Jpn J Pharmacol. 1992 Dec;60(4):335-40. doi: 10.1254/jjp.60.335.
DS-4574 is a peptidoleukotriene antagonist with mast cell stabilizing activity. In the present study, we studied the effects of this compound on gastric secretion and various acute gastric lesions in rats. Intraduodenal administration of DS-4574 at doses of 5 to 10 mg/kg significantly and dose-dependently inhibited gastric acid secretion in pylorus-ligated rats, but a further increase in the dose up to 50 mg/kg did not cause any further inhibition. Shay ulceration in response to pylorus ligation was dose-dependently prevented by DS-4574 (10-25 mg/kg, i.d.). Water-immersion restraint stress- and aspirin-induced gastric ulcers were also significantly prevented in a dose-related manner by oral pretreatment with DS-4574 (10-50 mg/kg). The lower doses of DS-4574 (1-10 mg/kg, p.o.) significantly and dose-dependently protected the gastric mucosa against the necrotizing action of either absolute ethanol or concentrated hydrochloric acid, indicating that this compound possesses a potent gastroprotective activity. These antiulcer and gastric protective effects of DS-4574 were more potent than those of cimetidine used as a reference drug. These findings suggest that DS-4574 is useful for peptic ulcer therapy, as well as for the therapy of various allergic diseases, including asthma.
DS - 4574是一种具有肥大细胞稳定活性的肽白三烯拮抗剂。在本研究中，我们研究了该化合物对大鼠胃分泌及各种急性胃损伤的影响。十二指肠内给予5至10mg/kg剂量的DS - 4574可显著且剂量依赖性地抑制幽门结扎大鼠的胃酸分泌，但剂量进一步增加至50mg/kg时并未产生进一步的抑制作用。DS - 4574（10 - 25mg/kg，十二指肠内给药）可剂量依赖性地预防幽门结扎引起的 Shay 溃疡。口服预处理DS - 4574（10 - 50mg/kg）也可剂量相关地显著预防水浸束缚应激和阿司匹林诱导的胃溃疡。较低剂量的DS - 4574（1 - 10mg/kg，口服）可显著且剂量依赖性地保护胃黏膜免受无水乙醇或浓盐酸的坏死作用，表明该化合物具有强大的胃保护活性。DS - 4574的这些抗溃疡和胃保护作用比用作参考药物的西咪替丁更强。这些发现表明，DS - 4574可用于消化性溃疡治疗，以及包括哮喘在内的各种过敏性疾病的治疗。
