Pharmacology of erenumab in human isolated coronary and meningeal arteries: Additional effect of gepants on top of a maximum effect of erenumab

Tessa de Vries, Eloísa Rubio-Beltrán, Antoon van den Bogaerdt, Ruben Dammers, A. H.Jan Danser, Josefin Snellman, Jeanine Bussiere, Antoinette MaassenVanDenBrink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background and Purpose: 

Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP-induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan.

Experimental Approach: 

Concentration–response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP-blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3 μM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations. 

Key Results: 

Erenumab shifted the concentration-response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab. 

Conclusions and Implications: 

Gepants have additional effects on top of erenumab for CGRP-induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis.

Original languageEnglish
Pages (from-to)1720-1733
Number of pages14
JournalBritish Journal of Pharmacology
Volume181
Issue number12
Early online date6 Feb 2024
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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