Toward a pragmatic migraine model for drug testing: I. Cilostazol in healthy volunteers.
BACKGROUND
A model for the testing of novel antimigraine drugs should ideally use healthy volunteers for ease of recruiting. Cilostazol 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. The hypothesis of the present study was that sumatriptan but not placebo is effective in cilostazol-induced headache in healthy individuals.


METHODS
In a double-blind, randomized, cross-over design, 30 healthy volunteers of both sexes received cilostazol 200 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
Cilostazol induced a reproducible headache in 90% of the participants. The headache had several migraine-like features in most individuals. Median peak headache score was 2 on the sumatriptan day and 3 on the placebo day (p = 0.17). There was no reduction in headache intensity two hours after sumatriptan (p = 0.97) and difference in AUC 0 to four hours between two experimental days was not significant (p = 0.18). On the placebo day eight participants took rescue medication compared to 3 on the sumatriptan day (p = 0.13).


CONCLUSIONS
Despite similarities with migraine headache, cilostazol-induced headache in healthy volunteers does not respond to sumatriptan.
Danish Headache Centre and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Denmark.
Emma Katrine
EK
Hansen
Danish Headache Centre and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Denmark.
Song
S
Guo
Danish Headache Centre and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Denmark.
Messoud
M
Ashina
Danish Headache Centre and Department of Neurology, University of Copenhagen, Glostrup University Hospital, Denmark Jes.olesen@regionh.dk.
Jes
J
Olesen
D000293:Adolescent; D000328:Adult; D000077407:Cilostazol; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006805:Human Experimentation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D018170:Sumatriptan / Q000627:therapeutic use*; D013777:Tetrazoles / Q000009:adverse effects*; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects*; D055815:Young Adult
D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D018170:Sumatriptan; D000077407:Cilostazol
Headache; human migraine model; migraine; pain; phosphodiesterase type 3