Calcitonin gene-related peptide receptor (CGRPR) (CGRPR)

The Calcitonin gene-related peptide receptor (CGRPR) is a heteromeric G protein-coupled receptor (GPCR) that plays a central role in the pathophysiology of migraine and other primary headache disorders (StatPearls, 2023). It is formed by the assembly of the calcitonin receptor-like receptor (CALCRL) and the receptor activity-modifying protein 1 (RAMP1), which creates the specific binding site for the CGRP neuropeptide (UniProt, 2024). Activation of the CGRPR in the trigeminovascular system triggers potent vasodilation, neurogenic inflammation, and the sensitization of pain-sensing neurons, facilitating the transmission of migraine-related pain (Nature Reviews Neurology, 2018). Therapeutics targeting this receptor include monoclonal antibodies like erenumab and small-molecule antagonists known as gepants, which are used for both the acute treatment and prevention of migraine (FDA, 2023). By blocking CGRP binding, these drugs effectively mitigate the vascular and nociceptive cascades that characterize headache attacks (PubMed, 2021). While the target has revolutionized migraine therapy, its widespread role in systemic vascular regulation necessitates caution regarding cardiovascular safety and gastrointestinal motility in specific patient populations (AHA, 2022).

Other names

CGRP receptorCalcitonin receptor-like receptor complexCALCRL:RAMP1 complexCalcitonin receptor-like receptorRAMP1

Antagonism of the receptor complex to block the binding and activity of the CGRP neuropeptide, thereby inhibiting neurogenic inflammation, trigeminal pain signaling, and excessive vasodilation (Nature Reviews Drug Discovery, 2018; FDA, 2020).