Category: signaling
Calcitonin gene-related peptide (CGRP) is a 37-aa neuropeptide released from trigeminal sensory afferents → vasodilation + neurogenic inflammation in the meningeal vasculature. Validated migraine target: CGRP elevation during migraine attack; IV CGRP triggers migraine in susceptible patients. Two therapeutic classes: (1) Small-molecule CGRP-R antagonists (gepants — rimegepant, ubrogepant, atogepant) for acute treatment + prophylaxis; (2) Biologics — anti-CGRP mAbs (fremanezumab, galcanezumab, eptinezumab) or anti-CGRP-R mAb (erenumab) for prevention. Triptans (sumatriptan, rizatriptan — covered in serotonin pathway) work upstream via 5-HT1B/1D agonism that reduces CGRP release; the two classes are complementary but mechanistically linked. Long-term CGRP blockade safety is being monitored (CGRP has physiologic vasodilator role in cardiac stress response).