title: Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew).
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.
authors.affiliation: Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Frankie H M
authors.initials: FH
authors.lastname: Cheng
authors.forename: Paul L R
authors.initials: PL
authors.lastname: Andrews
authors.forename: Benoit
authors.initials: B
authors.lastname: Moreaux
authors.forename: Man-P
authors.initials: MP
authors.lastname: Ngan
authors.forename: John A
authors.initials: JA
authors.lastname: Rudd
authors.forename: Tasia S W
authors.initials: TS
authors.lastname: Sam
authors.forename: Man-K
authors.initials: MK
authors.lastname: Wai
authors.forename: Christina
authors.initials: C
authors.lastname: Wan
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000440:Butanols / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004087:Dihydroergotamine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004224:Diterpenes; D004294:Domperidone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008293:Malates; D008784:Methysergide / Q000494:pharmacology; D008787:Metoclopramide / Q000494:pharmacology; D008881:Migraine Disorders / Q000517:prevention & control*; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines; D012430:Ruthenium Red / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012788:Shrews; D018170:Sumatriptan / Q000494:pharmacology; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000440:Butanols; D016861:Cyclooxygenase Inhibitors; D004224:Diterpenes; D008293:Malates; D010880:Piperidines; C400708:R116301; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D012430:Ruthenium Red; D004087:Dihydroergotamine; D017294:Ondansetron; D004294:Domperidone; D004155:Diphenhydramine; D018170:Sumatriptan; C024353:resiniferatoxin; D012601:Scopolamine; D008787:Metoclopramide; C071423:capsazepine; C042253:bemesetron; D002211:Capsaicin; D007213:Indomethacin; D008784:Methysergide