Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921542 | European Journal of Pharmacology | 2005 | 8 Pages |
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 μmol), (2R-trans)-4-[1-[3,5-bis(trifluromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-hydroxybutanedioate (R116301; 10-100 μmol/kg), and scopolamine (1 μmol/kg), but not by dihydroergotamine (0.3-3 μmol/kg), sumatriptan (1-10 μmol/kg), methysergide (1-10 μmol/kg), tropanyl 3,5-dichlorobenzoate (MDL72222; 3-30 μmol/kg), ondansetron (0.3-3 μmol/kg), metoclopramide (3-30 μmol/kg), domperidone (3-30 μmol/kg), diphenhydramine (1-10 μmol/kg), or indomethacin (3-30 μmol/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.
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Authors
Frankie H.M. Cheng, Paul L.R. Andrews, Benoit Moreaux, Man-P. Ngan, John A. Rudd, Tasia S.W. Sam, Man-K. Wai, Christina Wan,