[Characteristics of T-593, a novel antiulcer agent, and each of its enantiomers on pharmacodynamics].
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.
Arai
H
H
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Mori
Y
Y
Mizuo
M
M
Urata
N
N
Komae
N
N
Doi
Y
Y
D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D006635:Histamine H2 Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000897:Anti-Ulcer Agents; D006146:Guanidines; D006635:Histamine H2 Antagonists; D013450:Sulfones; C088837:T 593