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Randomized Controlled Trial
. 2019 Oct;59(9):1468-1480.
doi: 10.1111/head.13634. Epub 2019 Sep 18.

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

Mohammad Al-Mahdi Al-Karagholi  1 , Hashmat Ghanizada  2 , Jakob M Hansen  1 , Lene T Skovgaard  3 , Jes Olesen  1   2 , Henrik B W Larsson  4 , Faisal M Amin  1 , Messoud Ashina  1
Affiliations
Randomized Controlled Trial

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

Mohammad Al-Mahdi Al-Karagholi et al. Headache. 2019 Oct.

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.

Trial registration: ClinicalTrials.gov NCT03609008.

Keywords: BRL 34915; BRL 38227; headache; healthy volunteers; levcromakalim; middle meningeal artery; migraine; potassium channel openers.

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References

    1. Al-Karagholi MA-M, Hansen JM, Severinsen J, Jansen-Olesen I, Ashina M. The KATP channel in migraine pathophysiology: A novel therapeutic target for migraine. J Headache Pain. 2017;18:90.
    1. Ploug KB, Boni LJ, Baun M, Hay-Schmidt A, Olesen J, Jansen-Olesen I. K(ATP) channel expression and pharmacological in vivo and in vitro studies of the K(ATP) channel blocker PNU-37883A in rat middle meningeal arteries. Br J Pharmacol. 2008;154:72-81.
    1. Ploug KB, Amrutkar DV, Baun M, et al. K(ATP) channel openers in the trigeminovascular system. Cephalalgia. 2012;32:55-65.
    1. Ploug KB, Edvinsson L, Olesen J, Jansen-Olesen I. Pharmacological and molecular comparison of KATP channels in rat basilar and middle cerebral arteries. Eur J Pharmacol. 2006;553:254-262.
    1. Jansen-Olesen I, Mortensen CH, El-Bariaki N, Ploug KB. Characterization of KATP-channels in rat basilar and middle cerebral arteries: Studies of vasomotor responses and mRNA expression. Eur J Pharmacol. 2005;523:109-118.

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