Opening of ATP sensitive potassium channels causes migraine attacks with aura
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissionsoup.com..
Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in patients. In a randomized, double-blind, placebo-controlled, crossover study, 17 patients aged 21-59 years and diagnosed with migraine with aura exclusively were randomly allocated to receive an infusion of 0.05 mg/min levcromakalim or placebo (isotonic saline) on two different days (ClinicalTrials.gov, ID: NCT04012047). The primary end points were the difference in incidence of migraine attacks with or without aura, headache and the difference in the area under the curve for headache intensity scores (0-12 h). Seventeen patients completed the study. Fourteen of 17 (82%) patients developed migraine attacks with and without aura after levcromakalim compared with 1 of 17 (6%) after placebo (P < 0.001). Ten patients (59%) developed migraine with aura after levcromakalim compared with none after placebo (P = 0.002). One additional patient reported 'possible' aura, only partially fulfilling the criteria. Levcromakalim is likely a novel migraine aura-inducing substance in humans. These findings highlight the ATP-sensitive potassium channel as a shared target in migraine aura and migraine headache. Likely, ATP-sensitive potassium channel opening leads to triggering of aura and headache, respectively, via distinct mechanisms.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:144 |
|---|---|
| Enthalten in: |
Brain : a journal of neurology - 144(2021), 8 vom: 04. Sept., Seite 2322-2332 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Al-Karagholi, Mohammad Al-Mahdi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
0G4X367WA3 |
|---|
| Anmerkungen: |
Date Completed 14.12.2021 Date Revised 14.12.2021 published: Print ClinicalTrials.gov: NCT04012047 Citation Status MEDLINE |
|---|
| doi: |
10.1093/brain/awab136 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM323241840 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM323241840 | ||
| 003 | DE-627 | ||
| 005 | 20231225183750.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/brain/awab136 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1077.xml |
| 035 | |a (DE-627)NLM323241840 | ||
| 035 | |a (NLM)33768245 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Al-Karagholi, Mohammad Al-Mahdi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Opening of ATP sensitive potassium channels causes migraine attacks with aura |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.12.2021 | ||
| 500 | |a Date Revised 14.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT04012047 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in patients. In a randomized, double-blind, placebo-controlled, crossover study, 17 patients aged 21-59 years and diagnosed with migraine with aura exclusively were randomly allocated to receive an infusion of 0.05 mg/min levcromakalim or placebo (isotonic saline) on two different days (ClinicalTrials.gov, ID: NCT04012047). The primary end points were the difference in incidence of migraine attacks with or without aura, headache and the difference in the area under the curve for headache intensity scores (0-12 h). Seventeen patients completed the study. Fourteen of 17 (82%) patients developed migraine attacks with and without aura after levcromakalim compared with 1 of 17 (6%) after placebo (P < 0.001). Ten patients (59%) developed migraine with aura after levcromakalim compared with none after placebo (P = 0.002). One additional patient reported 'possible' aura, only partially fulfilling the criteria. Levcromakalim is likely a novel migraine aura-inducing substance in humans. These findings highlight the ATP-sensitive potassium channel as a shared target in migraine aura and migraine headache. Likely, ATP-sensitive potassium channel opening leads to triggering of aura and headache, respectively, via distinct mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a KATP channel | |
| 650 | 4 | |a cromakalim | |
| 650 | 4 | |a headache | |
| 650 | 4 | |a human models | |
| 650 | 4 | |a levcromakalim | |
| 650 | 7 | |a KATP Channels |2 NLM | |
| 650 | 7 | |a Vasodilator Agents |2 NLM | |
| 650 | 7 | |a Cromakalim |2 NLM | |
| 650 | 7 | |a 0G4X367WA3 |2 NLM | |
| 700 | 1 | |a Ghanizada, Hashmat |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Cherie Amalie Waldorff |e verfasserin |4 aut | |
| 700 | 1 | |a Hougaard, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Ashina, Messoud |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Brain : a journal of neurology |d 1945 |g 144(2021), 8 vom: 04. Sept., Seite 2322-2332 |w (DE-627)NLM000126292 |x 1460-2156 |7 nnns |
| 773 | 1 | 8 | |g volume:144 |g year:2021 |g number:8 |g day:04 |g month:09 |g pages:2322-2332 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/brain/awab136 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 144 |j 2021 |e 8 |b 04 |c 09 |h 2322-2332 | ||