Effect of YNS-15P, a new alpha-2 adrenoceptor antagonist, on stress-stimulated colonic propulsion in rats.
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.
Yamamoto
O
O
Discovery Research Laboratories II, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
Niida
H
H
Tajima
K
K
Shirouchi
Y
Y
Kyotani
Y
Y
Ueda
F
F
Kise
M
M
Kimura
K
K
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002368:Castor Oil; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology; D005772:Gastrointestinal Transit / Q000187:drug effects; D017829:Granisetron / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010528:Peristalsis / Q000187:drug effects*; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D014287:Trimebutine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018723:Bethanechol; D002368:Castor Oil; D003975:Diazepam; D017829:Granisetron; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; D013449:Sulfonamides; D014287:Trimebutine; C115706:YNS 15P; C082871:GR 113808