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Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries

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@article{a228f78e279e4da6a8f2aefaea00aea3,
title = "Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries",
abstract = "BACKGROUND: ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown.OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache.METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning.RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo.CONCLUSION: Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.",
author = "Al-Karagholi, {Mohammad Al-Mahdi} and Hashmat Ghanizada and Hansen, {Jakob M} and Skovgaard, {Lene T} and Jes Olesen and Larsson, {Henrik B W} and Amin, {Faisal M} and Messoud Ashina",
note = "{\textcopyright} 2019 American Headache Society.",
year = "2019",
doi = "10.1111/head.13634",
language = "English",
volume = "59",
pages = "1468--1480",
journal = "Headache",
issn = "0017-8748",
publisher = "Wiley-Blackwell Publishing, Inc",
number = "9",

}

RIS

TY - JOUR

T1 - Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries

AU - Al-Karagholi, Mohammad Al-Mahdi

AU - Ghanizada, Hashmat

AU - Hansen, Jakob M

AU - Skovgaard, Lene T

AU - Olesen, Jes

AU - Larsson, Henrik B W

AU - Amin, Faisal M

AU - Ashina, Messoud

N1 - © 2019 American Headache Society.

PY - 2019

Y1 - 2019

N2 - BACKGROUND: ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown.OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache.METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning.RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo.CONCLUSION: Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.

AB - BACKGROUND: ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown.OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache.METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning.RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo.CONCLUSION: Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.

U2 - 10.1111/head.13634

DO - 10.1111/head.13634

M3 - Journal article

C2 - 31535367

VL - 59

SP - 1468

EP - 1480

JO - Headache

JF - Headache

SN - 0017-8748

IS - 9

ER -

ID: 58919645