RP67580, a neurokinin1 receptor antagonist, decreased restraint stress-induced defecation in rat.
We investigated the possibility that substance P would mediate defecation in rats subjected to restraint-stress. The increases in fecal pellet output caused by restraint-stress were inhibited by a neurokinin (NK)1 receptor antagonist, RP67580 with an ED50 (95% confidence limits) value of 0.59 (0.54-0.65) mg/kg i.p. RP68651, the enantiomer of RP67580 devoid of affinity for NK1 receptors, had little effect on it. In contrast, (+/-)SR48968, an NK2 receptor antagonist, was without effect. Furthermore, capsaicin treatment (125 mg/kg i.p.) was inactive in this model. These results suggest that the activation of NK1 receptors and substance P released from intrinsic neurons of the colon would be involved in stress-induced defecation in rats.
Ikeda
K
K
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Miyata
K
K
Orita
A
A
Kubota
H
H
Yamada
T
T
Tomioka
K
K
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003672:Defecation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D013237:Stereoisomerism; D013315:Stress, Psychological / Q000523:psychology*; D013373:Substance P / Q000378:metabolism
D000700:Analgesics; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C073839:SR 48968; D002211:Capsaicin