No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine
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No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine. / Ernstsen, Charlotte; Christensen, Sarah L.; Olesen, Jes; Kristensen, David M.
In: Cephalalgia, Vol. 41, No. 3, 2021, p. 329-339.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine
AU - Ernstsen, Charlotte
AU - Christensen, Sarah L.
AU - Olesen, Jes
AU - Kristensen, David M.
N1 - Publisher Copyright: © International Headache Society 2020.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - additivity
KW - CGRP
KW - CGRP receptor antagonists
KW - Headache
KW - pain
KW - triptans
U2 - 10.1177/0333102420963857
DO - 10.1177/0333102420963857
M3 - Journal article
C2 - 33059476
AN - SCOPUS:85092605188
VL - 41
SP - 329
EP - 339
JO - Cephalalgia
JF - Cephalalgia
SN - 0800-1952
IS - 3
ER -
ID: 278495672