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

Mohammad Al-Mahdi Al-Karagholi, Hashmat Ghanizada, Jakob M Hansen, Lene T Skovgaard, Jes Olesen, Henrik B W Larsson, Faisal M Amin, Messoud Ashina

Journal: Headache 2020;59(9):1468-1480

PMID: 31535367

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Abstract

BACKGROUND

ATP-sensitive potassium (K ) 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 K channels can activate and sensitize the perivascular nociceptors.

Address: Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Glostrup Research Park, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Glostrup Research Park, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

DOI: 10.1111/head.13634

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MeSH Terms: Adult, Cromakalim, Double-Blind Method, Female, Headache, Humans, Ion Channel Gating, Male, Meningeal Arteries, Middle Cerebral Artery, Organ Specificity, Potassium Channels, Sumatriptan, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents, Young Adult