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Abstract Details

Erenumab (AMG334) An Antagonist to Canonical CGRP-Receptor Does Not Impair Vasodilatory or Contractile Responses to Other Agents In Human Isolated Cerebral Arteries
Headache
S17 - Headache: Clinical Trials I (1:11 PM-1:22 PM)
002
Calcitonin gene-related peptide (CGRP) is a neuronal transmitter involved in migraine pathophysiology and in other biological functions. Recently, a monoclonal antibody to the canonical CGRP receptor, erenumab (AMG334), showed significant prophylactic efficacy and favorable safety in phase II and III clinical trials for migraine.
Given that CGRP can mediate vasodilation, we investigated the effect of erenumab on vasoactive agent responses to CGRP and other mediators using isolated human cerebral and meningeal arteries in the presence/absence of various vasodilatory (e.g. CGRP) and of several vasocontractile mediators.
Ring segments of human isolated cerebral and meningeal arteries were mounted in a sensitive myograph. Functional responses were studied by first inducing pre-contraction with 30 mM potassium chloride (KCl), followed by administration of CGRP in increasing concentrations (0.1 nM–0.1 mM) in the absence/presence of different erenumab concentrations. Additionally, contractile responses to sumatriptan and dihydroergotamine, and relaxant responses to substance-P and nicardipine were examined.
30 mM KCl showed stable contraction and CGRP induced a concentration-dependent relaxation. We observed that (i) erenumab had no direct contractile or relaxant effects, (ii) pre-treatment with erenumab antagonized CGRP-induced relaxation in a competitive manner, (iii) relaxant responses to substance-P and nicardipine were unaffected in the presence of erenumab and (iv) the contraction induced by sumatriptan or dihydroergotamine were unmodified by erenumab.
Our findings demonstrate the specific inhibitory effect of erenumab of CGRP-induced relaxation, while it is not associated with vasoconstrictive effect and does not impact vasorelaxant or contractile responses of other relevant vasoactive agents in human biology.
Authors/Disclosures

PRESENTER
No disclosure on file
No disclosure on file
Cen Xu, PhD (Amgen Inc.) No disclosure on file
Josefin Snellman No disclosure on file
Lars Edvinsson No disclosure on file