Arai H, Mori Y, Mizuo M, Urata N, Komae N, Doi Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Nihon Yakurigaku Zasshi. 1998 Aug;112(2):107-16. 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.
T - 593由两种旋光异构体组成，即（-）-S和（+）-R。我们之前的报告表明，T - 593具有双相作用，即持久的抗分泌作用和对胃黏膜血流量（GMBF）的改善作用。在本研究中，我们比较了每种异构体对这些双相作用的单独效力。在用幽门结扎法研究的抗分泌作用中，（-）-S异构体表现出强烈抑制作用，而（+）-R异构体无作用，而（+）-R异构体可改善GMBF。这些结果表明消旋T - 593的双相作用分别源自每种异构体。（-）-S异构体强烈抑制急性胃黏膜损伤形成，效力与T - 593本身相当，而（+）-R异构体作用较小。然而，由乙酸诱导的慢性胃溃疡不能通过单一光学异构体治疗愈合，而消旋T - 593则显示出显著效果。这一结果表明，治愈慢性溃疡不仅需要抗分泌作用，还需要改善GMBF。T - 593的这一有趣特性有望提高溃疡愈合质量（QOUH），也可能预防溃疡复发。
