Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats

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-5 93 on ethanol-induced gastric damage in rats. Rats were given intraperitone al 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 gast ric damage. Gastric hemodynamics were assessed by reflectance spectrophotom etry 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-induce d gastric injury the same dose of racemic T-593 exerted the most potent ant i-ulcerative activity. Both (+)-(6)-T-593 and racemic T-593 increased gastr ic mucosal blood flow and abolished gastric mucosal blood flow stasis induc ed by 40 % ethanol. Although (-)-(S)-T-593, which antagonizes histamine H-2 -receptors, exerts an antiulcerative effect, (+)-(6)-T-593 also protects th e gastric mucosa from ethanol-induced Injury, possibly by influencing gastr ic mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H-2-receptors and by enhancing gastric circulation in rats.