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Characterisation of vasodilatory responses in the presence of the CGRP receptor antibody erenumab in human isolated arteries

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

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  2. Understanding side-effects of anti-CGRP and anti-CGRP receptor antibodies

    Research output: Contribution to journalLetterResearchpeer-review

  • Eloísa Rubio-Beltrán
  • Alejandro Labastida-Ramírez
  • Kristian A Haanes
  • Antoon van den Bogaerdt
  • Ad Jjc Bogers
  • Clemens Dirven
  • Ah Jan Danser
  • Cen Xu
  • Josefin Snellman
  • Antoinette MaassenVanDenBrink
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BACKGROUND: Migraine is associated with activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP) and dilation of dural arteries. Novel treatments target calcitonin gene-related peptide or its receptor, which are present in all vascular beds, raising cardiovascular concerns. Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine.

METHODS: We characterised the relaxant responses to CGRP in the absence and presence of erenumab (1 μM) in isolated human middle meningeal, internal mammary and (proximal and distal) coronary arteries. Furthermore, in human internal mammary arteries from cardiovascularly-compromised patients, we assessed the pharmacological specificity of erenumab by investigating whether the vasodilatory responses to acetylcholine, sodium nitroprusside, pituitary adenylate cyclase activating polypeptide-38 (PACAP), vasoactive intestinal peptide and nicardipine, along with the vasoconstrictor responses to dihydroergotamine, were modified by erenumab.

RESULTS: Calcitonin gene-related peptide induced concentration-dependent vasodilatory responses in all vessels studied that were significantly antagonised by erenumab. In human internal mammary arteries from cardiovascularly-compromised patients, the responses to acetylcholine, sodium nitroprusside, PACAP, vasoactive intestinal peptide, nicardipine and dihydroergotamine were unaffected by erenumab.

CONCLUSION: Erenumab inhibits calcitonin gene-related peptide-induced vasodilatory responses in human middle meningeal arteries, human internal mammary arteries and human coronary arteries. Moreover, erenumab shows functional specificity as no interaction was observed with the relaxant responses to several vasodilators, nor the dihydroergotamine-dependent vasoconstrictor responses.

Original languageEnglish
JournalCephalalgia : an international journal of headache
Volume39
Issue number14
Pages (from-to)1735-1744
Number of pages10
ISSN0333-1024
DOIs
Publication statusPublished - Dec 2019
Externally publishedYes

    Research areas

  • Cardiovascular safety, coronary arteries, mammary arteries, meningeal arteries, migraine

ID: 58349218