TY - JOUR T1 - Effect of YNS-15P, a New <em>Alpha</em>-2 Adrenoceptor Antagonist, on Stress-Stimulated Colonic Propulsion in Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 691 LP - 696 VL - 287 IS - 2 AU - Osamu Yamamoto AU - Hiromichi Niida AU - Koyuki Tajima AU - Yoshiaki Shirouchi AU - Yousuke Kyotani AU - Fusao Ueda AU - Masahiro Kise AU - Kiyoshi Kimura Y1 - 1998/11/01 UR - http://jpet.aspetjournals.org/content/287/2/691.abstract N2 - 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-methylmethanesulfonamide 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. The American Society for Pharmacology and Experimental Therapeutics ER -