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阿尔多克萨可改善功能性消化不良的病理生理机制——胃排空延迟和胃顺应性受损。

Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

作者信息

Asano Teita, Aida Shuji, Suemasu Shintaro, Tahara Kayoko, Tanaka Ken-ichiro, Mizushima Tohru

机构信息

Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

LTT Bio-Pharma Co., Ltd, Shiodome Building 3F, 1-2-20 Kaigan, Minato-ku, Tokyo 105-0022, Japan.

出版信息

Sci Rep. 2015 Dec 1;5:17519. doi: 10.1038/srep17519.

Abstract

Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

摘要

胃排空延迟和胃容受功能受损(胃顺应性降低)在功能性消化不良(FD)中起重要作用。在此,我们筛选一种临床上使用的、具有改善大鼠胃排空延迟能力的药物。口服醛氧淀粉(二羟丙茶碱铝)可部分改善可乐定或束缚应激诱导的胃排空延迟。给予尿囊素而非氢氧化铝可恢复胃排空。醛氧淀粉和尿囊素均抑制可乐定与α-2肾上腺素能受体的结合,提示醛氧淀粉中尿囊素部分对该受体的拮抗活性与胃排空活性的恢复有关。醛氧淀粉或氢氧化铝而非尿囊素可恢复束缚应激下的胃顺应性,提示氢氧化铝部分参与了这种恢复。我们提出醛氧淀粉是FD的候选药物,因为其在人体中的安全性已得到证实,且在此证实了其对胃排空延迟和胃容受功能受损均有改善作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2f6/4664916/57fe83401c70/srep17519-f1.jpg

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