CGRP and its receptors

Headache. 2017 Apr;57(4):625-636. doi: 10.1111/head.13064. Epub 2017 Feb 24.


The calcitonin gene-related peptide (CGRP) neuropeptide system is an important but still evolving target for migraine. A fundamental consideration for all of the current drugs in clinical trials and for ongoing development in this area is the identity, expression pattern, and function of CGRP receptors because this knowledge informs safety and efficacy considerations. In recent years, only the calcitonin receptor-like receptor/receptor activity-modifying protein 1 (RAMP1) complex, known as the CGRP receptor, has generally been considered relevant. However, CGRP is capable of activating multiple receptors and could have more than one endogenous receptor. The recent identification of the CGRP-responsive calcitonin receptor/RAMP1 complex (AMY1 receptor - amylin subtype 1 receptor) in the trigeminovascular system warrants a deeper consideration of the molecular identity of CGRP receptor(s) involved in the pathophysiology, and thus potential treatment of migraine. This perspective considers some of the issues and implications.

Keywords: CGRP; amylin; migraine; receptor activity-modifying protein.

MeSH terms

  • Brain / metabolism*
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcitonin Receptor-Like Protein / antagonists & inhibitors
  • Calcitonin Receptor-Like Protein / genetics
  • Calcitonin Receptor-Like Protein / metabolism*
  • Humans
  • Migraine Disorders / drug therapy
  • Migraine Disorders / genetics
  • Migraine Disorders / metabolism
  • Models, Molecular
  • Receptors, Calcitonin Gene-Related Peptide / genetics*
  • Receptors, Calcitonin Gene-Related Peptide / immunology*


  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcitonin Receptor-Like Protein
  • Receptors, Calcitonin Gene-Related Peptide