RP67580, a neurokinin1 receptor antagonist, decreased restraint stress-induced defecation in rat

Neurosci Lett. 1995 Sep 29;198(2):103-6. doi: 10.1016/0304-3940(95)11972-y.

Abstract

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.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Benzamides / pharmacology
  • Capsaicin / pharmacology
  • Defecation / drug effects*
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology*
  • Isoindoles
  • Male
  • Neurokinin-1 Receptor Antagonists*
  • Piperidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Restraint, Physical
  • Stereoisomerism
  • Stress, Psychological / psychology*
  • Substance P / metabolism

Substances

  • Analgesics
  • Benzamides
  • Indoles
  • Isoindoles
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Receptors, Neurokinin-2
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Substance P
  • SR 48968
  • Capsaicin