Tsuji S, Kawano S, Tsujii M, Kawai N, Gunawan E S, Sun W H, Hori M
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan.
Arzneimittelforschung. 2001 Jan;51(1):46-50. doi: 10.1055/s-0031-1300001.
T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.
T-593（奥舒替丁，CAS 140695-21-2）是一种新型抗溃疡药物，由两种对映体组成，即(+)-(R)-T-593和(-)-(S)-T-593。本研究旨在探究T-593、(+)-(R)-T-593和(-)-(S)-T-593对乙醇诱导的大鼠胃损伤的影响。给大鼠腹腔注射溶媒、消旋T-593、(+)-(R)-T-593或(-)-(S)-T-593。30分钟后，给大鼠胃内灌入1毫升40%乙醇溶液，30分钟后处死大鼠以评估胃损伤情况。实验过程中通过反射分光光度法和激光多普勒血流仪评估胃血流动力学。消旋T-593以剂量依赖性方式显著抑制胃损伤。虽然60毫克/千克的(+)-(R)-T-593和(-)-(S)-T-593也能抑制乙醇诱导的胃损伤，但相同剂量的消旋T-593具有最强的抗溃疡活性。(+)-(R)-T-593和消旋T-593均增加胃黏膜血流量，并消除40%乙醇诱导的胃黏膜血流淤滞。虽然拮抗组胺H2受体的(-)-(S)-T-593具有抗溃疡作用，但(+)-(R)-T-593也可能通过影响胃黏膜血流动力学保护胃黏膜免受乙醇诱导的损伤。因此，消旋T-593可能通过拮抗H2受体和增强大鼠胃循环来保护胃黏膜。
