Calcitonin Gene-Related Peptide (CGRP) is a 37-amino-acid neuropeptide and one of the most potent vasodilators known. It is the target of FDA-approved migraine therapeutics including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small-molecule antagonists (rimegepant, ubrogepant). CGRP itself is endogenous and released by trigeminal sensory neurons during migraine attacks. The therapeutic strategy is to block CGRP or its receptor, not to administer it. This makes CGRP unique among peptides on this platform — the clinical interest is in its antagonism.
Category: Pain / Migraine. Evidence rating: A (strong human clinical data).
Clinical status: Endogenous peptide. Anti-CGRP therapies are FDA-approved for migraine prevention and treatment. CGRP itself is not a therapeutic.
CGRP is released from trigeminal sensory nerve endings during migraine and binds to the CGRP receptor complex (CLR + RAMP1) on meningeal blood vessels and trigeminal neurons. This triggers vasodilation, neurogenic inflammation, mast cell degranulation, and central sensitization — the key…
Safety considerations: CGRP itself is not administered therapeutically; safety data pertains to anti-CGRP drugs; Anti-CGRP antibodies: generally well-tolerated; injection site reactions, constipation, and rare hypersensitivity are the main adverse effects; CGRP has cardioprotective and wound-healing roles; long-term CGRP blockade raises theoretical concerns about cardiovascular risk and impaired wound healing.
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | 37 amino acids (α-CGRP) |
|---|---|
| Molecular weight | ~3789 g/mol |
| Half-life | ~6.9 minutes (rapid enzymatic degradation) |
| Production method | bioactive |
| Anti-doping status | not-listed |
| US regulatory status | CGRP is an endogenous peptide. Anti-CGRP therapies are FDA-approved: erenumab (2018), fremanezumab (2018), galcanezumab (2018), rimegepant (2020), ubrogepant (2019), eptinezumab (2020). |
No — you want CGRP blockers, not CGRP itself. CGRP causes migraines; drugs like erenumab (Aimovig), fremanezumab (Ajovy), and rimegepant (Nurtec) work by blocking CGRP or its receptor. Talk to a neurologist about whether anti-CGRP therapy is appropriate for you.
CGRP is included because it is one of the most clinically significant peptides in medicine. The anti-CGRP drug class represents the most successful peptide-targeted therapy development in recent decades and illustrates how understanding a peptide's biology can lead to breakthrough treatments.
CGRP has cardioprotective and vasodilatory roles. Long-term blockade theoretically could impair cardiovascular compensation during ischemia. However, 5+ years of post-marketing data from anti-CGRP drugs has not revealed major cardiovascular safety signals.
No. Anti-CGRP therapies are preventive — they reduce migraine frequency and severity but do not cure the underlying condition. Most patients still experience some migraines, and the benefit stops when treatment is discontinued.
Yes, in research contexts. CGRP has wound-healing, cardioprotective, and anti-hypertensive properties. Some researchers are exploring CGRP agonism for conditions like Raynaud's disease and critical limb ischemia, though this is early-stage.
Coverage on this site: Amylins (IAPP): Structure, Receptors, and Key Analogues.