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

Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Intradural artery dilation during experimentally induced migraine attacks

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Mechanistic pain profiling in young adolescents with patellofemoral pain before and after treatment: a prospective cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Neck pain and headache after whiplash injury: a systematic review and meta-analysis

    Research output: Contribution to journalReviewResearchpeer-review

  1. CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Hormonal influences in migraine - interactions of oestrogen, oxytocin and CGRP

    Research output: Contribution to journalReviewResearchpeer-review

  3. Pre-Chiasmatic, Single Injection of Autologous Blood to Induce Experimental Subarachnoid Hemorrhage in a Rat Model

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Identifying New Antimigraine Targets: Lessons from Molecular Biology

    Research output: Contribution to journalReviewResearchpeer-review

  • Alejandro Labastida-Ramírez
  • Eloísa Rubio-Beltrán
  • Kristian A Haanes
  • Kayi Y Chan
  • Ingrid M Garrelds
  • Kirk W Johnson
  • Alexander H J Danser
  • Carlos M Villalón
  • Antoinette MaassenVanDenBrink
View graph of relations

Migraine headache pathophysiology involves trigeminovascular system activation, calcitonin gene-related peptide (CGRP) release, and dysfunctional nociceptive transmission. Triptans are 5-HT1B/1D/(1F) receptor agonists that prejunctionally inhibit trigeminal CGRP release, but their vasoconstrictor properties limit their use in migraine patients with cardiovascular disease. By contrast, lasmiditan is a novel antimigraine and selective 5-HT1F receptor agonist devoid of vasoconstrictor properties. On this basis, this study has investigated the modulation of trigeminal CGRP release by lasmiditan. For this purpose, we have comparatively analysed the inhibition of several components of the trigeminovascular system induced by lasmiditan and sumatriptan through: ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion, and trigeminal nucleus caudalis of mice; and in vivo dural vasodilation in the rat closed-cranial window model induced by endogenous (electrical stimulation and capsaicin) and exogenous CGRP. The ex vivo release of CGRP was similarly inhibited by sumatriptan and lasmiditan in all trigeminovascular system components. In vivo, intravenous (i.v.) lasmiditan or higher doses of sumatriptan significantly attenuated the vasodilatory responses to endogenous CGRP release, but not exogenous CGRP effects. These data suggest that lasmiditan prejunctionally inhibits CGRP release in peripheral and central trigeminal nerve terminals. Because lasmiditan is a lipophilic drug that crosses the blood-brain barrier, additional central sites of action remain to be determined.

Original languageEnglish
JournalPain
Volume161
Issue number5
Pages (from-to)1092-1099
Number of pages8
ISSN0304-3959
DOIs
Publication statusPublished - May 2020
Externally publishedYes

ID: 60210168