Calcitonin gene-related peptide receptor type 1 (CGRPR)

The Calcitonin gene-related peptide receptor type 1 (CGRPR) is a unique heteromeric G protein-coupled receptor (GPCR) consisting of the calcitonin receptor-like receptor (CLR), the receptor activity-modifying protein 1 (RAMP1), and a receptor component protein (RCP) [Source: UniProt, P30988]. It is widely expressed in the central and peripheral nervous systems, particularly within the trigeminovascular system, where it mediates the potent vasodilatory and pro-nociceptive effects of the CGRP neuropeptide [Source: PubMed, PMC6134863]. Activation of the CGRPR leads to increased intracellular cAMP levels, contributing to neurogenic inflammation and the sensitization of pain pathways associated with migraine and cluster headaches [Source: StatPearls, NBK553136]. Pharmacological targeting of this receptor has revolutionized migraine therapy, with drugs like erenumab (a monoclonal antibody) and small-molecule gepants (e.g., rimegepant, ubrogepant) acting as potent antagonists [Source: FDA, Drug Labels]. These therapies prevent the binding of CGRP to its receptor, thereby inhibiting the cascade that leads to headache pain and associated symptoms [Source: Nature Reviews Drug Discovery, 2018]. While generally well-tolerated, safety considerations include potential effects on blood pressure and gastrointestinal motility due to the receptor's role in systemic vasodilation and smooth muscle relaxation [Source: PubMed, PMC6734421].

Other names

CGRP receptorCALCRL:RAMP1 complexCalcitonin receptor-like receptor complexCGRP1 receptor

Competitive antagonism of the CGRP receptor complex, specifically blocking the binding site of the CGRP neuropeptide to prevent activation of the Gs-protein signaling pathway and subsequent cAMP production.