Kosaka N, Tanaka H, Tomaru A, Ishii A, Shuto K
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1994 Aug;65(4):305-12. doi: 10.1254/jjp.65.305.
Effects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent-induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 = 1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50 = 4.5-39.8 mg/kg, p.o.). In addition, the cytoprotective effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.
将新型抗溃疡药物KW - 5805对大鼠各种实验性溃疡、坏死剂诱导的胃损伤及胃酸分泌的影响，与哌仑西平和西咪替丁进行了比较。KW - 5805对实验性胃溃疡和十二指肠溃疡显示出抗溃疡活性（口服半数有效剂量ED50 = 1.2 - 10.0 mg/kg）。KW - 5805能有效抑制多种坏死剂诱导的胃损伤（口服半数有效剂量ED50 = 4.5 - 39.8 mg/kg）。此外，KW - 5805的细胞保护作用不受吲哚美辛影响，但可被N - 乙基马来酰亚胺抑制。KW - 5805的这些抗溃疡和细胞保护作用比哌仑西平和西咪替丁更强。在幽门结扎大鼠中，十二指肠内给予30 mg/kg的KW - 5805显示出较弱的抗分泌作用，其效力比哌仑西平和西咪替丁低3 - 10倍。在急性胃瘘大鼠中，静脉注射10和30 mg/kg剂量的KW - 5805可减少乙酰甲胆碱刺激的胃酸分泌，30 mg/kg剂量时可抑制四肽胃泌素诱导的胃酸分泌。这些结果表明，KW - 5805具有强大而广泛的抗溃疡特性，这可能是由于其除了抗分泌作用外还具有强大的细胞保护作用。
