Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

Cephalalgia. 2010 Oct;30(10):1233-40. doi: 10.1177/0333102410362122. Epub 2010 Mar 26.


Introduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology.

Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining.

Results: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries.

Conclusions: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.

MeSH terms

  • Aged
  • Azepines / pharmacology*
  • Calcitonin Gene-Related Peptide Receptor Antagonists*
  • Calcitonin Receptor-Like Protein
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Imidazoles / pharmacology*
  • Immunohistochemistry
  • Male
  • Meningeal Arteries / drug effects*
  • Middle Aged
  • Receptor Activity-Modifying Protein 1 / drug effects
  • Receptor Activity-Modifying Protein 1 / metabolism
  • Receptors, Calcitonin / drug effects
  • Receptors, Calcitonin / metabolism
  • Vasodilation / drug effects


  • Azepines
  • CALCRL protein, human
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcitonin Receptor-Like Protein
  • Imidazoles
  • RAMP1 protein, human
  • Receptor Activity-Modifying Protein 1
  • Receptors, Calcitonin
  • telcagepant