title: Towards a pragmatic human migraine model for drug testing: 2. Isosorbide-5-mononitrate in healthy individuals.
abstract: Background A model for the testing of novel anti-migraine drugs should preferably use healthy volunteers for ease of recruiting. Isosorbide-5-mononitrate (5-ISMN) provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity. Therefore, this headache might respond to sumatriptan, a requirement for validation of any model. The hypothesis of the present study was that sumatriptan is effective in 5-ISMN-induced headache in healthy individuals. Methods In a double-blind, randomised, crossover design, 30 healthy volunteers of both sexes received 5-ISMN 60 mg on two separate days, each day followed by oral self-administered placebo or sumatriptan 50 mg. Headache response and accompanying symptoms were registered in a questionnaire by the participants themselves. Results 5-ISMN induced a reproducible headache in all 30 participants. The headache had several migraine-like features in all participants and 20 individuals developed a migraine-like attack. Median peak headache score was 5 on both experimental days ( p = 1.00). There was no reduction, but instead an increase in headache intensity 2 hours after sumatriptan ( p = 0.003). Difference in area under the headache score curve (AUC) 0-4 hours between sumatriptan and placebo was not significant ( p = 0.30). Conclusion 5-ISMN is a very powerful inducer of migraine-like headache in healthy individuals but the headache does not respond to sumatriptan. The model is not useful for future drug testing.
authors.affiliation: Danish Headache Centre and Department of Neurology, University of Copenhagen, Rigshospitalet Glostrup, Denmark.
authors.forename: Emma Katrine
authors.initials: EK
authors.lastname: Hansen
authors.affiliation: Danish Headache Centre and Department of Neurology, University of Copenhagen, Rigshospitalet Glostrup, Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D008954:Models, Biological; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D018170:Sumatriptan / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000633:toxicity*
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D014665:Vasodilator Agents; D018170:Sumatriptan; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate
keywords: Headache; human migraine model; migraine; nitric oxide; pain