Characterization of two models of drug-induced constipation in mice and evaluation of mustard oil in these models

Pharmacology. 2009;84(4):227-33. doi: 10.1159/000236524. Epub 2009 Sep 10.

Abstract

Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 microg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Clonidine
  • Constipation / chemically induced*
  • Constipation / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Gastrointestinal Transit / drug effects*
  • Indoles / pharmacology
  • Loperamide
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mustard Plant
  • Naloxone / pharmacology
  • Plant Oils / therapeutic use*
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / agonists
  • Yohimbine / pharmacology

Substances

  • Indoles
  • Plant Oils
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Yohimbine
  • Naloxone
  • tegaserod
  • Loperamide
  • Atropine
  • Clonidine
  • mustard oil