Evaluation of the anti-emetic potential of anti-migraine drugs to prevent resiniferatoxin-induced emesis in Suncus murinus (house musk shrew).
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.
Cheng
Frankie H M
FH
Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Andrews
Paul L R
PL
Moreaux
Benoit
B
Ngan
Man-P
MP
Rudd
John A
JA
Sam
Tasia S W
TS
Wai
Man-K
MK
Wan
Christina
C
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*
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