Characteristics of T-593, a novel antiulcer agent, and each of its enantiomers on pharmacodynamics

• Published in: Nihon yakurigaku zasshi Vol. 112; no. 2; p. 107
• Main Authors: Arai, H, Mori, Y, Mizuo, M, Urata, N, Komae, N, Doi, Y
• Format: Journal Article
• Language: Japanese
• Published: Japan 1998
• Subjects: Animals; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Anti-Ulcer Agents - toxicity; Dose-Response Relationship, Drug; Gastric Mucosa - blood supply; Guanidines - chemistry; Guanidines - pharmacology; Guanidines - toxicity; Histamine H2 Antagonists - chemistry; Histamine H2 Antagonists - pharmacology; Histamine H2 Antagonists - toxicity; Lethal Dose 50; Male; Peptic Ulcer - chemically induced; Peptic Ulcer - drug therapy; Rats; Rats, Sprague-Dawley; Rats, Wistar; Regional Blood Flow - drug effects; Stereoisomerism; Structure-Activity Relationship; Sulfones - chemistry; Sulfones - pharmacology; Sulfones - toxicity
• ISSN: 0015-5691
• DOI: 10.1254/fpj.112.107

T-593 consists of two optical isomers, (-)-S and (+)-R. Our previous report showed that T-593 has biphasic effects, that is a long-lasting antisecretory action and an improving effect on gastric mucosal blood flow (GMBF). In this study, we compared the sole potency of each isomer on these bi-phasic effects. On the anti-secretory action investigated by the pylorus-ligation method, the (-)-S-isomer showed strong inhibition, while the (+)-R-isomer showed no effect, whereas the GMBF improvement was provided by the (+)-R-isomer. These results show the bi-phasic effects of racemic T-593 are separately derived from each isomer. The (-)-S-isomer strongly inhibited acute gastric mucosal lesion formation, with a potency comparable to T-593 itself, while the (+)-R-isomer showed less effect. Chronic gastric ulcer induced by acetic acid was, however, not healed by the sole treatment of each optical isomer, while racemic T-593 showed a significant effect. This result shows not only anti-secretion but also GMBF improvement is necessary to heal the chronic ulcer. This interesting property of T-593 is expected to raise the quality of ulcer healing (QOUH) and also may prevent ulcer recurrence.