Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew)

Eur J Pharmacol. 2005 Jan 31;508(1-3):231-8. doi: 10.1016/j.ejphar.2004.12.022. Epub 2005 Jan 6.

Abstract

Activation of vanilloid receptors has commonly been used to facilitate neurogenic inflammation and plasma exudation to model components of the pathogenesis of migraine; however, these studies have been performed mainly in species lacking the emetic reflex. In the present studies, therefore, we used Suncus murinus, a species of insectivore capable of emesis, to investigate if the vanilloid receptor agonist resiniferatoxin is capable of modeling the emesis associated with migraine. Resiniferatoxin (100 nmol/kg, s.c.) induced an emetic response that was antagonized significantly (P<0.05) by ruthenium red (1-3 micromol), (2R-trans)-4-[1-[3,5-bis(trifluromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-hydroxybutanedioate (R116301; 10-100 micromol/kg), and scopolamine (1 micromol/kg), but not by dihydroergotamine (0.3-3 micromol/kg), sumatriptan (1-10 micromol/kg), methysergide (1-10 micromol/kg), tropanyl 3,5-dichlorobenzoate (MDL72222; 3-30 micromol/kg), ondansetron (0.3-3 micromol/kg), metoclopramide (3-30 micromol/kg), domperidone (3-30 micromol/kg), diphenhydramine (1-10 micromol/kg), or indomethacin (3-30 micromol/kg). The failure of a wide range of representative anti-migraine drugs to reduce retching and vomiting limits the use of this model to identify/investigate novel treatments for the emesis (and nausea) associated with migraine attacks in humans. However, the results provide further evidence for the involvement of a novel vanilloid receptor in resiniferatoxin-induced emesis and implicate both tachykinins and acetylcholine in the pathway(s) activated by resiniferatoxin in S. murinus.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiemetics / pharmacology*
  • Butanols / pharmacology
  • Capsaicin / analogs & derivatives*
  • Capsaicin / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Dihydroergotamine / pharmacology
  • Diphenhydramine / pharmacology
  • Diterpenes
  • Domperidone / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Indomethacin / pharmacology
  • Malates
  • Methysergide / pharmacology
  • Metoclopramide / pharmacology
  • Migraine Disorders / prevention & control*
  • Ondansetron / pharmacology
  • Piperidines
  • Ruthenium Red / pharmacology
  • Scopolamine / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Shrews
  • Sumatriptan / pharmacology
  • Time Factors
  • Tropanes / pharmacology
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Butanols
  • Cyclooxygenase Inhibitors
  • Diterpenes
  • Malates
  • Piperidines
  • R116301
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Tropanes
  • Ruthenium Red
  • Dihydroergotamine
  • Ondansetron
  • Domperidone
  • Diphenhydramine
  • Sumatriptan
  • resiniferatoxin
  • Scopolamine
  • Metoclopramide
  • capsazepine
  • bemesetron
  • Capsaicin
  • Indomethacin
  • Methysergide