Chapter 24  ·  Module 5
CGRP Pharmacology and Migraine Therapeutics
Migraine mechanism, gepant and antibody drug classes, and cardiovascular safety
Calcitonin Gene-Related Peptide in Migraine
Trigger
Trigeminal Activation
Sensory neurons innervating meningeal vessels activated
Release
CGRP Released
Elevated in jugular blood during migraine attack
Effects
Meningeal Effects
Vasodilation + neurogenic inflammation + pain sensitization
Result
Migraine Pain
Central sensitization — allodynia in established migraine
CGRP Drug Classes vs Triptans — Key Comparisons
Feature Ubrogepant Rimegepant Atogepant Erenumab Fremanezumab / Galcanezumab / Eptinezumab
Class Gepant Gepant Gepant Monoclonal antibody Monoclonal antibody
Target CGRP receptor CGRP receptor (RAMP1) CGRP peptide
Acute use Yes Yes No No No
Preventive use No Yes Yes Yes Yes
Route Oral Oral (ODT) Oral SC monthly SC monthly/quarterly; IV quarterly (eptinezumab)
Vasoconstriction No No No No No
Safe in CV disease Yes Yes Yes Caution* Caution*
Key adverse effect Nausea Nausea Constipation, nausea Constipation, injection site reaction Injection site reaction
* Caution: patients with recent MI or stroke excluded from pivotal trials — safety in active CV disease not fully characterized.