Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks: A randomized clinical trial
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Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks : A randomized clinical trial. / Kokoti, Lili; Al-Karagholi, Mohammad Al Mahdi; Zhuang, Zixuan Alice; Amirguliyev, Sarkhan; Amin, Faisal Mohammad; Ashina, Messoud.
I: Cephalalgia : an international journal of headache, Bind 44, Nr. 5, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks
T2 - A randomized clinical trial
AU - Kokoti, Lili
AU - Al-Karagholi, Mohammad Al Mahdi
AU - Zhuang, Zixuan Alice
AU - Amirguliyev, Sarkhan
AU - Amin, Faisal Mohammad
AU - Ashina, Messoud
PY - 2024
Y1 - 2024
N2 - OBJECTIVE: To investigate the role of NN414, a selective KATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and β-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. METHODS: Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo. The secondary endpoints were the difference in the area under the curve for headache intensity scores, middle cerebral artery blood flow velocity (VMCA), superficial temporal artery diameter, heart rate and mean arterial pressure. RESULTS: Twelve participants completed the study, with two (16.6%) reporting migraine attacks after NN414 compared to one (8.3%) after placebo (p = 0.53). The area under the curve for headache intensity, VMCA, superficial temporal artery diameter, heart rate and mean arterial pressure did not differ between NN414 and placebo (p > 0.05, all comparisons). CONCLUSION: The lack of migraine induction upon activation of the Kir6.2/SUR1 channel subtype suggests it may not contribute to migraine pathogenesis. Our findings point to KATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments.Registration number: NCT04744129.
AB - OBJECTIVE: To investigate the role of NN414, a selective KATP channel opener for the Kir6.2/SUR1 channel subtype found in neurons and β-pancreatic cells, in inducing migraine attacks in individuals with migraine without aura. METHODS: Thirteen participants were randomly allocated to receive NN414 and placebo on two days separated by at least one week. The primary endpoint was the difference in the incidence of migraine attacks after NN414 compared with placebo. The secondary endpoints were the difference in the area under the curve for headache intensity scores, middle cerebral artery blood flow velocity (VMCA), superficial temporal artery diameter, heart rate and mean arterial pressure. RESULTS: Twelve participants completed the study, with two (16.6%) reporting migraine attacks after NN414 compared to one (8.3%) after placebo (p = 0.53). The area under the curve for headache intensity, VMCA, superficial temporal artery diameter, heart rate and mean arterial pressure did not differ between NN414 and placebo (p > 0.05, all comparisons). CONCLUSION: The lack of migraine induction upon activation of the Kir6.2/SUR1 channel subtype suggests it may not contribute to migraine pathogenesis. Our findings point to KATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments.Registration number: NCT04744129.
KW - headache
KW - human models
KW - KATP channel
KW - levcromakalim
KW - NN414
KW - tifenazoxide
U2 - 10.1177/03331024241248211
DO - 10.1177/03331024241248211
M3 - Journal article
C2 - 38729773
AN - SCOPUS:85192950465
VL - 44
JO - Cephalalgia
JF - Cephalalgia
SN - 0800-1952
IS - 5
ER -
ID: 392569020