An important advance in the treatment of migraine has been the development of agents that target calcitonin gene-related peptide (CGRP), a neuropeptide that has emerged as a key player in the neurobiology of migraine.
The CGRP family comprises calcitonin, CGRP, adrenomedullin and amylin (Walker et al. Br J Pharmacol 2013;170:1293-1307). The receptors consist of one G protein-coupled receptor, either calcitonin receptor (CTR) or the calcitonin-like receptor (CLR), linked to a receptor activity-modifying protein (RAMP). Different combinations of these subunits result in functional receptors for CGRP (CLR + RAMP1), adrenomedullin (CLR + RAMP2 or RAMP3) and amylin (CTR + RAMP1, RAMP2 or RAMP3) (Hay et al. Br J Pharmacol 2018;175:3-17). There are two isoforms of CGRP: the alpha form, which is primarily found in the central and peripheral nervous systems, most notably the trigeminal ganglion and the dorsal root ganglion; and the beta form, which is mostly present in the enteric nervous system (Juaneda et al. Trends Pharmacol Sci 2000;21:432-438).