Peptide Basics
CGRP (Calcitonin Gene-Related Peptide): What It Is, Its Receptor, the Migraine Link and What FDA Records Show
CGRP, calcitonin gene-related peptide, is a 37-amino-acid neuropeptide made by nerve cells from the same gene as the hormone calcitonin, and one that MeSH describes as a potent endogenous vasodilator, a substance that widens blood vessels. This page sets out how one gene gives both calcitonin and CGRP, how alpha- and beta-CGRP differ, how its two-part receptor works, what the early research found about CGRP and migraine, and the eight CGRP-pathway medicines in FDA’s records, with what each label says it blocks. Every figure is taken from UniProt, PubChem, MeSH, PubMed or FDA’s own databases and labels.
What CGRP is
MeSH, the U.S. National Library of Medicine’s subject index, describes calcitonin gene-related peptide as a 37-amino-acid peptide that results from alternative processing of the messenger RNA of the calcitonin gene. It is widely distributed in the brain, the gut, the nerves that wrap around blood vessels and other tissue; it acts both in the circulation and as a nerve signal; and, in MeSH’s words, it is in particular a potent endogenous vasodilator. It is one of the neuropeptides, the peptides that nerve cells release to signal.
It was found from the gene before anyone had isolated the peptide. In 1982 Amara and colleagues reported in Nature that RNA from the calcitonin gene is processed in two ways: one message encodes the thyroid hormone calcitonin, the other a predicted product they named calcitonin gene-related peptide; the calcitonin message predominated in the thyroid and the CGRP message in the hypothalamus (PMID 6283379). A year later Rosenfeld and colleagues reported that nerve tissue makes the new peptide and, from where CGRP-producing cells sit in the brain, suggested roles in pain signalling, eating behaviour and the autonomic and endocrine systems (PMID 6346105).
Sources: MeSH D015740; UniProt P06881; PubMed 6283379 and 6346105. Read 12 November 2026.
Alpha-CGRP and beta-CGRP: two genes, one shape
Humans make two forms. Both are cut from a longer precursor after a signal sequence and a propeptide are removed, both are 37 amino acids long, and UniProt records the same structure for each: a ring formed by a bond between the cysteines at positions 2 and 7, and a final phenylalanine carrying an amide group.
| Form | Gene | Positions in the precursor | Sequence (37 amino acids) |
|---|---|---|---|
| Alpha-CGRP (CGRP1) | CALCA, the calcitonin gene | 83-119 of a 128-amino-acid precursor | ACDTATCVTHRLAGLLSRSGGVVKNNFVPTNVGSKAF |
| Beta-CGRP (CGRP2) | CALCB, a separate gene | 82-118 of a 127-amino-acid precursor | ACNTATCVTHRLAGLLSRSGGMVKSNFVPTNVGSKAF |
Set side by side, the two human sequences differ at three positions: 3 (aspartate in alpha, asparagine in beta), 22 (valine or methionine) and 25 (asparagine or serine). UniProt records the same vasodilator function for both and the same receptor; it lists the spinal cord as a site of both, and the pituitary and thalamus for beta-CGRP. Only alpha-CGRP comes from the calcitonin gene itself. PubChem gives human alpha-CGRP the formula C163H269N51O49S2 and a molecular weight of 3,791.3 (CID 16132372).
Sources: UniProt P06881 and P10092 (sequence comparison ours); PubChem CID 16132372. Read 12 November 2026.
The CGRP receptor: one protein, three partners
The CGRP receptor is a pair. MeSH records that it forms when the calcitonin receptor-like receptor (CALCRL, 461 amino acids) joins receptor activity-modifying protein 1 (RAMP1), and that CGRP receptors sit both in the brain and spinal cord and in the rest of the body. The partner decides what the receptor answers to. In 1998 McLatchie and colleagues showed that CALCRL works as a CGRP receptor when RAMP1 carries it to the cell surface, and as a receptor for the related peptide adrenomedullin when RAMP2 does (PMID 9620797). UniProt records that the receptor then activates the cAMP pathway inside the cell.
| Pair | Answers to | Note |
|---|---|---|
| CALCRL + RAMP1 | CGRP (alpha and beta) | The CGRP receptor. UniProt records that RAMP1 is needed to carry CALCRL to the cell surface. |
| CALCRL + RAMP2 | Adrenomedullin | The same receptor protein with a different partner answers a different peptide. |
| CALCRL + RAMP3 | Adrenomedullin | A second adrenomedullin receptor. |
| CALCR + RAMP1 (AMYR1) | Amylin and alpha-CGRP | A calcitonin-receptor complex that UniProt records alpha-CGRP can also bind and activate. |
The overlap explains why CGRP, calcitonin, amylin and adrenomedullin are studied as one family: they share receptor parts. Our calcitonin page sets out the calcitonin-receptor side of the same system. MeSH describes adrenomedullin as a 52-amino-acid peptide and a potent vasodilator, first isolated from the adrenal medulla.
Sources: MeSH D018015, D058286, D058262 and D053607; UniProt Q16602, O60894, O60895, P06881; PubMed 9620797. Read 12 November 2026.
What CGRP does: blood vessels, nerves and the migraine finding
- Blood vessels. In 1985 Brain and colleagues reported in Nature that CGRP is a potent vasodilator: very small amounts in the skin increased local blood flow in rabbits, it caused persistent local reddening in human skin, and it relaxed strips of rat aorta by a mechanism that needed the vessel’s inner lining (PMID 3917554). UniProt records that CGRP widens coronary, cerebral and systemic vessels.
- Nerves. UniProt notes that its abundance in the brain and spinal cord points to a role as a neurotransmitter or neuromodulator, and MeSH files the medicines that block its receptor as agents that block pain signalling from CGRP receptors. It is often studied alongside substance P, another sensory-nerve peptide.
- Migraine. In 1990 Goadsby, Edvinsson and Ekman measured four vasoactive peptides in people during migraine attacks. CGRP was substantially raised in blood from the external jugular vein, which drains the head, but not in blood from the arm, more so in migraine with aura than without, while neuropeptide Y, vasoactive intestinal polypeptide and substance P were unchanged (PMID 1699472). The authors wrote that the finding may matter for how migraine arises; the medicines below came almost three decades later.
Sources: PubMed 3917554 and 1699472 (abstracts); UniProt P06881; MeSH D000077221. Read 12 November 2026.
CGRP in FDA’s records: the antibodies and the gepants
Drugs@FDA, searched by active ingredient on 12 November 2026, holds eight brand medicines that act on the CGRP pathway, all first approved between 2018 and 2023. They come in two kinds. Four are monoclonal antibodies, large proteins licensed as biologics; their labels say one of them binds the CGRP receptor and three bind the CGRP peptide itself and stop it reaching the receptor. Four are small molecules whose names share the ending “-gepant”; each label calls its drug a CGRP receptor antagonist. None of the eight is itself a peptide hormone.
| Product | Application | Approved | What it blocks (label) | Indication (label) |
|---|---|---|---|---|
| Aimovig (erenumab-aooe) | BLA 761077 | 2018 | Antibody that binds the CGRP receptor | Preventive treatment of migraine in adults. |
| Ajovy (fremanezumab-vfrm) | BLA 761089 | 2018 | Antibody that binds the CGRP peptide itself | Preventive treatment of migraine in adults, and of episodic migraine in some patients aged 6 to 17 named on the label. |
| Emgality (galcanezumab-gnlm) | BLA 761063 | 2018 | Antibody that binds the CGRP peptide itself | Preventive treatment of migraine in adults; treatment of episodic cluster headache in adults. |
| Vyepti (eptinezumab-jjmr) | BLA 761119 | 2020 | Antibody that binds the CGRP peptide itself | Preventive treatment of migraine in adults. |
| Ubrelvy (ubrogepant) | NDA 211765 | 2019 | Small-molecule CGRP receptor antagonist | Acute treatment of migraine with or without aura in adults; not indicated for prevention. |
| Nurtec ODT (rimegepant) | NDA 212728 | 2020 | Small-molecule CGRP receptor antagonist | Acute treatment of migraine with or without aura, and preventive treatment of episodic migraine, in adults. |
| Qulipta (atogepant) | NDA 215206 | 2021 | Small-molecule CGRP receptor antagonist | Preventive treatment of migraine in adults. |
| Zavzpret (zavegepant) | NDA 216386 | 2023 | Small-molecule CGRP receptor antagonist | Acute treatment of migraine with or without aura in adults; not indicated for prevention. |
The indications differ: the antibodies and atogepant are labelled for preventing migraine, ubrogepant and zavegepant for treating an attack and expressly not for prevention, and rimegepant for both. Galcanezumab is also labelled for episodic cluster headache. PubChem gives rimegepant a molecular weight of 534.6, ubrogepant 549.5 and atogepant 603.5, each less than a sixth of CGRP’s 3,791.3. This page reports what the labels say; it does not compare how well the medicines work.
Sources: Drugs@FDA via openFDA, searched by active ingredient (original approval dates; data updated 10 November 2026); current U.S. labels, sections 1, 11 and 12.1, for Aimovig (July 2026), Ajovy, Emgality and Vyepti (June 2026), Ubrelvy (September 2026), Nurtec ODT (April 2026), Qulipta (September 2025) and Zavzpret (December 2025); PubChem CID 51049968, 68748835 and 72163100. Read 12 November 2026. Doses are not reproduced here; the approved medicines that are themselves peptides are on our FDA-approved peptides page.
Medibact does not manufacture or sell peptides. We supply USP-grade bacteriostatic water, made in the USA, for research use only, and publish reference material like this page.
Where this sits in the rest of the reference
FAQ
What is CGRP?
CGRP, calcitonin gene-related peptide, is a 37-amino-acid neuropeptide. MeSH describes it as a peptide made from the calcitonin gene by alternative processing of its messenger RNA, widely distributed in the brain, gut, the nerves around blood vessels and other tissue, with both circulatory and neurotransmitter modes of action, and in particular a potent endogenous vasodilator, meaning it widens blood vessels.
What does CGRP do?
UniProt records that CGRP widens a variety of blood vessels, including the coronary, cerebral and systemic circulation, through the CALCRL-RAMP1 receptor, and that its abundance in the brain and spinal cord points to a role as a neurotransmitter or neuromodulator. When it was first described in 1983, its authors suggested functions in pain signalling, eating behaviour and the autonomic and endocrine systems (PubMed 6346105).
How is CGRP related to calcitonin?
They come from the same gene, CALCA. In 1982 Amara and colleagues showed that the gene's RNA is processed in two ways: one message encodes the thyroid hormone calcitonin, the other a predicted peptide they called calcitonin gene-related peptide; the calcitonin message predominated in the thyroid and the CGRP message in the hypothalamus (PubMed 6283379). The two peptides share receptor parts but do different jobs.
What is the difference between alpha-CGRP and beta-CGRP?
They are made by two different genes: alpha-CGRP by CALCA, the calcitonin gene, and beta-CGRP by CALCB. Both are 37 amino acids long with the same ring between positions 2 and 7 and the same amidated end; their human sequences differ at three positions (3, 22 and 25). UniProt records the same vasodilator function for both, through the same receptor.
What is the CGRP receptor?
A pair of proteins: the calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1). In 1998 McLatchie and colleagues showed that CALCRL acts as a CGRP receptor when paired with RAMP1 and as a receptor for a related peptide, adrenomedullin, when paired with RAMP2 (PubMed 9620797). UniProt records that the receptor activates the cAMP pathway inside the cell.
What does CGRP have to do with migraine?
A key early finding was a 1990 study by Goadsby, Edvinsson and Ekman, who measured four vasoactive peptides in blood during migraine attacks: CGRP was substantially raised in blood from the external jugular vein, which drains the head, but not in blood from the arm, and the other three peptides were unchanged (PubMed 1699472). The medicines approved since 2018 that block CGRP or its receptor are all indicated for migraine, as their labels state.
What are CGRP inhibitors?
A common name for the medicines that block the CGRP pathway. FDA's records hold two kinds: four monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab) and four small-molecule receptor antagonists (ubrogepant, rimegepant, atogepant and zavegepant). Their labels describe each one as a CGRP antagonist or a CGRP receptor antagonist. None of them is itself a peptide hormone.
Do all CGRP medicines work the same way?
No. By their labels, erenumab binds the CGRP receptor, while fremanezumab, galcanezumab and eptinezumab bind the CGRP peptide itself and stop it reaching the receptor. The four small molecules block the receptor. The labels also differ in what they are indicated for: some for preventing migraine, some for treating an attack, one for both and one also for episodic cluster headache. This page reports the labels; choosing or comparing treatments belongs with a clinician.
What is adrenomedullin?
A related 52-amino-acid peptide that MeSH describes as a potent vasodilator first isolated from the adrenal medulla. It shares CGRP's receptor protein, CALCRL, but with a different partner: UniProt records that CALCRL with RAMP2 or RAMP3 forms the adrenomedullin receptors, and with RAMP1 the CGRP receptor.
Is this medical advice?
No. This page explains what CGRP is, from public scientific and regulatory sources. It gives no dose, schedule or recommendation and does not compare how well medicines work; anyone with headaches or taking a medicine named here should follow their own clinician and product label. Peptides sold for research are labelled research use only, not for human use. Medibact supplies USP-grade bacteriostatic water, made in the USA, and is not affiliated with any manufacturer of the products named here.
References: UniProt P06881, P10092, Q16602, O60894, O60895; MeSH D015740, D018015, D000077221, D058262, D058286, D053607; PubChem CID 16132372, 51049968, 68748835, 72163100; PubMed 6283379, 6346105, 3917554, 1699472, 9620797; Drugs@FDA via openFDA and the current U.S. labels named above. Read 12 November 2026.
Educational use only — not medical advice. This guide summarizes information reported in published research and community practice for educational purposes. It is not medical advice and not a recommendation to use any compound. Any doses, schedules, or combinations shown are examples of what has been reported, not instructions for you. Many peptides described here are research compounds that are not FDA-approved for the uses discussed and may be investigational or restricted. Effects, risks, and legal status vary; individual needs and results vary. Consult a qualified, licensed healthcare professional before making any decision. Do not use this content to diagnose, treat, or dose yourself.