Yamamoto O, Niida H, Tajima K, Shirouchi Y, Kyotani Y, Ueda F, Kise M, Kimura K
Discovery Research Laboratories II, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
J Pharmacol Exp Ther. 1998 Nov;287(2):691-6.
We studied effects of a novel alpha-2 adrenoceptor antagonist, YNS-15P (N-[(2R,11bS)-9-methoxy-1,3,4,6,7, 11b-hexahydro-2H-benzoquinolizin-2-yl]-N-methylmethanesulfonami de hydrochloride), on colonic propulsion stimulated by wrap-restraint stress (WRS) or bethanechol, on normal colonic propulsion and on diarrhea induced by castor oil in rats. Alpha-2 adrenoceptor antagonists, rauwolscine and RX821002, decreased the increase in the number and weight of fecal pellets induced by WRS. YNS-15P also inhibited WRS-stimulated fecal excretion in a dose-dependent manner. A 5-hydroxytryptamine3 receptor antagonist, granisetron, trimebutine and diazepam, but not a 5-hydroxytryptamine4 receptor antagonist, GR113808, significantly inhibited WRS-stimulated fecal excretion. YNS-15P inhibited WRS-stimulated colonic transit in a dose-dependent manner. However, YNS-15P had no significant effect on normal fecal excretion and colonic transit or on bethanechol-stimulated fecal excretion. YNS-15P also failed to inhibit castor-oil-induced diarrhea. These results indicate that YNS-15P selectively inhibits WRS-stimulated colonic propulsion, and that alpha-2 adrenoceptors may be involved in stress-induced colonic motor dysfunction in fed rats.
我们研究了一种新型α-2肾上腺素能受体拮抗剂YNS-15P（N-[(2R,11bS)-9-甲氧基-1,3,4,6,7,11b-六氢-2H-苯并喹嗪-2-基]-N-甲基甲磺酰胺盐酸盐）对束缚应激（WRS）或氨甲酰甲胆碱刺激的结肠推进、正常结肠推进以及蓖麻油诱导的大鼠腹泻的影响。α-2肾上腺素能受体拮抗剂萝芙辛和RX821002可减少WRS诱导的粪便颗粒数量和重量的增加。YNS-15P也以剂量依赖的方式抑制WRS刺激的粪便排泄。5-羟色胺3受体拮抗剂格拉司琼、曲美布汀和地西泮可显著抑制WRS刺激的粪便排泄，但5-羟色胺4受体拮抗剂GR113808则无此作用。YNS-15P以剂量依赖的方式抑制WRS刺激的结肠转运。然而，YNS-15P对正常粪便排泄和结肠转运或氨甲酰甲胆碱刺激的粪便排泄无显著影响。YNS-15P也未能抑制蓖麻油诱导的腹泻。这些结果表明，YNS-15P选择性抑制WRS刺激的结肠推进，且α-2肾上腺素能受体可能参与了进食大鼠应激诱导的结肠运动功能障碍。
