RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 691
OP 696
VO 287
IS 2
A1 Yamamoto, Osamu
A1 Niida, Hiromichi
A1 Tajima, Koyuki
A1 Shirouchi, Yoshiaki
A1 Kyotani, Yousuke
A1 Ueda, Fusao
A1 Kise, Masahiro
A1 Kimura, Kiyoshi
YR 1998
UL http://jpet.aspetjournals.org/content/287/2/691.abstract
AB 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