Non-vascular ATP-sensitive potassium channel activation does not trigger migraine attacks: A randomized clinical trial.

Autor: Kokoti L; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Al-Karagholi MA; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Zhuang ZA; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Amirguliyev S; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Amin FM; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ashina M; Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Danish Headache Knowledge Center, Rigshospitalet - Glostrup, Glostrup, Denmark.
Jazyk: angličtina
Zdroj: Cephalalgia : an international journal of headache [Cephalalgia] 2024 May; Vol. 44 (5), pp. 3331024241248211.
DOI: 10.1177/03331024241248211
Abstrakt: Objective: To investigate the role of NN414, a selective K ATP 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 (V MCA ), 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, V MCA , 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 K ATP channel blockers that target the Kir6.1/SUR2B subtype, found in cerebral vasculature, as potential candidates for innovative antimigraine treatments. Registration number: NCT04744129.
Competing Interests: Declaration of conflicting interestsLK, MMK, SA and ZAZ report no conflicts of interests. FMA has received honoraria or personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, Teva for lecturing and/or participation in advisory boards; serves as president of Danish Headache Society and board member of the European Headache Federation; serves as junior associate editor for Acta Neurol Scand, Front Neurol, Front Res Pain, and Headache Medicine; serves as junior associate editor for Cephalalgia and Cephalalgia Reports; serves as member for the editorial board of Journal Headache Pain. MA reports receiving personal fees from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals during the conduct of the study. MA also reports serving as associate editor of The Journal of Headache and Pain, and associate editor of Brain.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje