1. Academic Validation
  2. No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine

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

  • Cephalalgia. 2021 Mar;41(3):329-339. doi: 10.1177/0333102420963857.
Charlotte Ernstsen 1 Sarah L Christensen 1 Jes Olesen 1 David M Kristensen 1 2
Affiliations

Affiliations

  • 1 Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.
  • 2 University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.
Abstract

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.

Keywords

CGRP; CGRP receptor antagonists; Headache; additivity; pain; triptans.

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