Towards a pragmatic human migraine model for drug testing: 2. Isosorbide-5-mononitrate in healthy individuals

TY - JOUR

T1 - Towards a pragmatic human migraine model for drug testing

T2 - 2. Isosorbide-5-mononitrate in healthy individuals

AU - Hansen, Emma Katrine

AU - Olesen, Jes

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Adult

KW - Cross-Over Studies

KW - Double-Blind Method

KW - Female

KW - Healthy Volunteers

KW - Humans

KW - Isosorbide Dinitrate/analogs & derivatives

KW - Male

KW - Middle Aged

KW - Migraine Disorders/chemically induced

KW - Models, Biological

KW - Serotonin 5-HT1 Receptor Agonists/therapeutic use

KW - Sumatriptan/therapeutic use

KW - Vasodilator Agents/toxicity

U2 - 10.1177/0333102416636095

DO - 10.1177/0333102416636095

M3 - Journal article

C2 - 26924839

SN - 0333-1024

VL - 37

SP - 11

EP - 19

JO - Cephalalgia : an international journal of headache

JF - Cephalalgia : an international journal of headache

IS - 1

ER -