CGRP

also known as: Calcitonin Gene-Related Peptide, α-CGRP, β-CGRP

The migraine molecule — the most powerful vasodilator in the body and the key mediator of migraine pain, targeted by the blockbuster anti-CGRP drug class (erenumab, galcanezumab, fremanezumab, rimegepant).

A 37-amino-acid neuropeptide released from trigeminal sensory neurons during migraine, acting on CLR/RAMP1 receptor complexes to cause meningeal vasodilation and neurogenic inflammation, directly targeted by anti-CGRP monoclonal antibodies and gepant small molecules.

Mechanism of action

Released from trigeminal C-fibers during cortical spreading depression (migraine aura) or via trigeminovascular activation. Binds the CLR/RAMP1 receptor complex (calcitonin receptor-like receptor complexed with RAMP1), activating Gs → cAMP. Causes potent meningeal arteriolar vasodilation, mast cell degranulation, plasma protein extravasation, and peripheral and central sensitization. The most potent vasodilator known: 10× more potent than prostaglandins.

Primary uses

Migraine pathophysiology research
Target of anti-CGRP therapeutics
Cardiovascular vasodilation studies
Cluster headache research

Typical dosing

Not established

Endogenous neuropeptide. IV CGRP infusion used experimentally to provoke migraine in research (1.5 mcg/min × 20 min). Not a therapeutic.

Regulatory status

CGRP itself is not administered therapeutically. Anti-CGRP pathway drugs FDA-approved: erenumab (Aimovig, anti-CGRP receptor mAb, 2018), galcanezumab (Emgality, anti-CGRP mAb, 2018), fremanezumab (Ajovy, anti-CGRP mAb, 2018), eptinezumab (Vyepti, anti-CGRP mAb, 2020), rimegepant (Nurtec, CGRP receptor antagonist, 2020), ubrogepant (Ubrelvy, 2019), atogepant (Qulipta, 2021).

References

[review] Edvinsson L, et al. "CGRP as the target of new migraine therapies — successful translation from bench to clinic." Nat Rev Neurol, 2018;14:338-350.
[pubmed] Russell FA, et al. "Calcitonin gene-related peptide: physiology and pathophysiology." Physiol Rev, 2014;94:1099-1142.

Related peptides

Calcitonin

The bone-protective thyroid hormone — a 32-amino-acid peptide that directly inhibits osteoclasts, used as a nasal spray or injection for osteoporosis and hypercalcemia.

Adrenomedullin

A multi-organ protective peptide — a potent vasodilator and emerging sepsis biomarker (MR-proADM) with roles in cardiac, pulmonary, and renal protection.

Substance P

The pain and nausea neuropeptide — an 11-amino-acid tachykinin that transmits pain signals and triggers vomiting, targeted by aprepitant (Emend) and the entire NK1 antagonist drug class.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.