No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Charlotte Ernstsen
  • Sarah L. Christensen
  • Olesen, Jes
  • David M. Kristensen

Introduction: Despite recent advances in migraine treatment there is a need for therapies with higher clinical efficacy and/or fewer side effects. Triptans (5-HT1B/1D/1F agonists) are essential in the present treatment regime and gepants (CGRP-receptor antagonists) are recognized as effective in acute migraine treatment. Triptans and gepants have different mechanisms of action and here we tested the hypothesis that a combination of these drugs (sumatriptan and olcegepant) would result in an additive effect. Methods: Using the validated glyceryl trinitrate mouse model of migraine, we initially tested dose-response relationships of sumatriptan (0.1, 0.3, and 0.6 mg/kg IP) and olcegepant (0.25, 0.50, and 1.0 mg/kg IP) to find suitable high and low doses. Subsequently, we performed a combination study of the two drugs with a low and a high dose. All experiments were vehicle (placebo) controlled and blinded. Results: Sumatriptan significantly reduced glyceryl trinitrate-induced allodynia (F(4,54) = 13.51, p < 0.0001) at all doses. Olcegepant also reduced glyceryl trinitrate-induced allodynia (F(4,53) = 16.11, p < 0.0001) with the two higher doses being significantly effective. Combining 0.50 mg/kg olcegepant with 0.1 or 0.6 mg/kg sumatriptan did not have any improved effect compared to either drug alone (p > 0.50 on all days) in our mouse model. Conclusion: Combining olcegepant and sumatriptan did not have an additive effect compared to single-drug treatment in this study. Triptan-gepant combinations will therefore most likely not improve migraine treatment. Nevertheless, further studies are necessary, and combinations should also be examined in patients with migraine.

OriginalsprogEngelsk
TidsskriftCephalalgia
Vol/bind41
Udgave nummer3
Sider (fra-til)329-339
Antal sider11
ISSN0333-1024
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support was provided by the Candys Foundation.

Publisher Copyright:
© International Headache Society 2020.

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