Nagakura Yukinori, Kiso Tetsuo, Miyata Keiji, Ito Hiroyuki, Iwaoka Kiyoshi, Yamaguchi Tokio
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Life Sci. 2002 Aug 2;71(11):1313-9. doi: 10.1016/s0024-3205(02)01841-6.
The effect of the selective 5-hydroxytryptamine (5-HT)(3) receptor agonist YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate) on gut motility of fed ferrets was investigated. YM-31636 (0.1 mg/kg p.o.) induced a giant migrating contraction (GMC)-like, high-amplitude, ungrouped colonic contraction although it did not change the basal colonic motility pattern. This GMC-like contraction was always accompanied by defecation. Both GMC-like contraction and defecation were inhibited with the selective 5-HT(3) receptor antagonist ramosetron. YM-31636 affected gastric, duodenal and ileal motility pattern only slightly. These results suggest that 5-HT(3) receptor agonists such as YM-31636 are useful in treating constipation since they facilitate GMC-like contractions and defecation without undesired changes in gut motility pattern.
研究了选择性5-羟色胺（5-HT）（3）受体激动剂YM-31636（2-（1H-咪唑-4-基甲基）-8H-茚并[1,2-d]噻唑单富马酸盐）对喂食雪貂肠道运动的影响。口服0.1mg/kg的YM-31636可诱发类似巨移行收缩（GMC）的高振幅、非成组的结肠收缩，尽管它并未改变基础结肠运动模式。这种类似GMC的收缩总是伴有排便。选择性5-HT（3）受体拮抗剂雷莫司琼可抑制类似GMC的收缩和排便。YM-31636对胃、十二指肠和回肠运动模式的影响很小。这些结果表明，像YM-31636这样的5-HT（3）受体激动剂可用于治疗便秘，因为它们促进类似GMC的收缩和排便，而不会引起肠道运动模式的不良变化。
