Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

ATP sensitive potassium (KATP) channel inhibition: A promising new drug target for migraine

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Low plasma levels of calcitonin gene-related peptide in persistent post-traumatic headache attributed to mild traumatic brain injury

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Neurofilament light chain as biomarker in idiopathic intracranial hypertension

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Functional gene networks reveal distinct mechanisms segregating in migraine families

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. No central action of CGRP antagonising drugs in the GTN mouse model of migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: Recently, the adenosine triphosphate (ATP) sensitive potassium channel opener levcromakalim was shown to induce migraine attacks with a far higher incidence than any previous provoking agent such as calcitonin gene-related peptide. Here, we show efficacy of ATP sensitive potassium channel inhibitors in two validated rodent models of migraine.

METHODS: In female spontaneous trigeminal allodynic rats, the sensitivity of the frontal region of the head was tested by an electronic von Frey filament device. In mice, cutaneous hypersensitivity was induced by repeated glyceryl trinitrate or levcromakalim injections over nine days, as measured with von Frey filaments in the hindpaw. Release of calcitonin gene-related peptide from dura mater and trigeminal ganglion was studied ex vivo.

RESULTS: The ATP sensitive potassium channel inhibitor glibenclamide attenuated the spontaneous cephalic hypersensitivity in spontaneous trigeminal allodynic rats and glyceryl trinitrate-induced hypersensitivity of the hindpaw in mice. It also inhibited CGRP release from dura mater and the trigeminal ganglion isolated from spontaneous trigeminal allodynic rats. The hypersensitivity was also diminished by the structurally different ATP sensitive potassium channel inhibitor gliquidone. Mice injected with the ATP sensitive potassium channel opener levcromakalim developed a progressive hypersensitivity that was completely blocked by glibenclamide, confirming target engagement.

CONCLUSION: The results suggest that ATP sensitive potassium channel inhibitors could be novel and highly effective drugs in the treatment of migraine.

Original languageEnglish
JournalCephalalgia : an international journal of headache
Volume40
Issue number7
Pages (from-to)650-664
Number of pages15
ISSN0333-1024
DOIs
Publication statusPublished - 2020

ID: 60054569