Peptide LibraryPACAP-38
Also known as: Pituitary adenylate cyclase-activating polypeptide-38
PACAP-38 (also called Pituitary adenylate cyclase-activating polypeptide-38) is an endogenous neuropeptide in the VPAC/PAC1 agonist class. Pituitary adenylate cyclase-activating polypeptide is a 38-amino-acid neuropeptide closely related to vasoactive intestinal peptide, sharing roughly two-thirds sequence identity. It binds the PAC1 receptor with high selectivity and also engages VPAC1 and VPAC2; all are Gs-coupled, so activation raises cyclic AMP in neurons and endocrine cells.
For research use only.
Key Facts
- CAS
- 137061-48-4
- Molecular Weight (MW)
- ≈4534 g/mol
- Half-life
- Very short; rapidly degraded by peptidases
- FDA status
- Not Approved
- Evidence level
- Limited Human Evidence
- Human dose established
- No
- Administration Route
- Not established in humans
- Frequency
- Not established in humans
- Last updated
- Nov 7, 2026
- Reviewed
- Nov 7, 2026
- Targets
- PAC1VPAC1VPAC2
Research summary
38-aa neuropeptide that activates PAC1/VPAC receptors. Research tool in migraine, neuroprotection, and metabolic models. Not FDA-approved as a drug.
Research evidence
- Regulatory review (FDA label)None in reviewed sources
- Controlled human trials3 reviewed sources
- Early or uncontrolled human studiesNone in reviewed sources
- Lab & animal studiesNone in reviewed sources
How it works
Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.
Peptide Library's PACAP-38 profile summarises 5 cited studies listed in the Science section, the compound's regulatory status, and research-protocol parameters reported for it. It is a research reference, not medical advice.
PACAP-38 dosage: no established human dose
PACAP-38 has no established human dosage. People have received it only in short laboratory infusions used to study headache and blood flow, in the studies reviewed here 10 pmol/kg per minute into a vein, for 20 minutes where stated. It causes headache in most people, and delayed migraine-like attacks in many people with migraine, so these studies use it to provoke symptoms, not to treat anything.
No established human dosage.
Human clinical evidence: None identified.
Preclinical research: PACAP-38 is a natural neuropeptide that is broken down quickly in the blood. Human use is limited to infusions in a hospital research setting, given in picomoles per kilogram per minute to trigger headache and widen blood vessels so that migraine can be studied. The studies reviewed here gave it only by intravenous infusion to provoke symptoms; none tested it as a treatment, so no therapeutic human dose exists.
Animal dosing is not converted into a human dose anywhere on this page. Where research figures appear below, they are reported as studied, not recommended.
| Human dosing established | No |
|---|---|
| Route | Intravenous infusion (experimental studies only) |
| Evidence level | Limited Human Evidence |
| Last reviewed | 2026-11-07 |
Human research reported
Doses as studied, one row per regimen. Different trials used different regimens; they are listed separately rather than averaged.
| Study / context | Population | Dose | Route | Frequency | Duration | Outcome studied | Source |
|---|---|---|---|---|---|---|---|
| Cerebral blood flow study in healthy volunteers (Birk et al. 2007)Clinical trial · Double-blind, placebo-controlled crossover physiology study | Healthy young volunteers (n=12) | 10 pmol/kg per minute, or saline placebo | Intravenous infusion | Single infusion on each study day | 20 minutes | No major direct effect on regional cerebral blood flow; heart rate rose by about 62%, which the authors called a dose-limiting factor | The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers. Regul Pept. 2007. |
| Migraine provocation study (Schytz et al. 2009)Clinical trial · Randomised, double-blind, placebo-controlled crossover provocation study | 12 healthy people and 12 people with migraine without aura | 10 pmol/kg per minute, or placebo | Intravenous infusion | Single infusion on each study day | Infusion length not stated in the indexed abstract | Headache in all healthy people and 11 of 12 with migraine; 7 of 12 with migraine had migraine-like attacks after PACAP-38 and none after placebo, mostly hours later | PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain. 2009. |
| PACAP-38 provocation after eptinezumab (Al-Karagholi et al. 2025, NCT05635604)Clinical trial · Randomised, double-blind, placebo-controlled parallel-group study | Adults with migraine without aura (n=38) | 10 pmol/kg per minute, 2 hours after eptinezumab 300 mg or placebo | Intravenous infusion | Single infusion | 20 minutes | Migraine attacks in 10 of 19 after eptinezumab and 12 of 19 after placebo, no significant difference; no serious adverse events | PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial. J Headache Pain. 2025. |
Where sources disagree
- The 10 pmol/kg per minute infusion is a headache-provocation model, not a dose for any benefit. It caused headache in nearly everyone tested and sharply raised heart rate.
- PACAP-27, the shorter form, and vasoactive intestinal peptide have their own provocation studies. They are different peptides, and their results are not evidence for PACAP-38.
Reconstitution
These figures are arithmetic only — they convert a vial and a volume into a concentration. They are not a recommendation to take any dose.
Calculate reconstitution & dose →Sequence & molecular data
| Molecular formula | C203H331N63O53S |
|---|---|
| Molecular weight | ≈4534 g/mol |
| CAS number | 137061-48-4 |
| Half-life | Very short; rapidly degraded by peptidases |
| Appearance | White lyophilized powder |
| Formulation | Lyophilized Powder |
| PubChem CID | 91935803 |
Identifiers link to the public PubChem, FDA Substance Registration (UNII), ChEMBL and DrugBank records for the same entity.
Science
Mechanism of Action
Pituitary adenylate cyclase-activating polypeptide is a 38-amino-acid neuropeptide closely related to vasoactive intestinal peptide, sharing roughly two-thirds sequence identity. It binds the PAC1 receptor with high selectivity and also engages VPAC1 and VPAC2; all are Gs-coupled, so activation raises cyclic AMP in neurons and endocrine cells. Reported roles include neurotrophic and neuroprotective signalling, regulation of catecholamine release from the adrenal medulla, and circadian modulation. It has a distinctive place in human research because intravenous infusion reliably triggers migraine-like headache in susceptible people, which established the PACAP pathway as a migraine target and led to therapeutic antibodies against it.
Origin
Endogenous neuropeptide; synthetic research material.
Targets
Studies
- PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial
- Part I: Pituitary adenylate cyclase-activating polypeptide-38 induced migraine-like attacks in patients with and without familial aggregation of migraine
- PACAP-38 is increased in the tear fluid of patients with migraine
- Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache
- Pituitary adenylate cyclase-activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells
Research statistics
3,895 PubMed publications · 4.5% human clinical research · 13 registered trials
Counts of published research through 2026-11-01, not evidence that it works. Publications by year, study types and trials · How publications are counted
Regulatory & research status
PACAP-38 is not an FDA-approved product. It is sold for laboratory research and has no approved medical use.
| FDA status | Not Approved |
|---|---|
| Availability | Research-Only |
| WADA (sport) | Unknown / Not Listed |
| Library classification | Research-Only |
How FDA approval, compounding and research-only status differ
Benefits
PACAP-38 side effects
PACAP-38 has only limited human data, so the list below is incomplete and its side-effect profile is not well established.
Side Effects
- Flushing
- Headache / migraine provocation
Storage & stability
Lyophilized (freeze-dried) peptide powder is far more stable than the reconstituted solution. Keep sealed vials cold, dry and away from light; long-term storage is typically frozen, with short-term refrigeration for vials in use.
Once reconstituted in bacteriostatic water, keep the solution refrigerated, avoid repeated freeze–thaw cycles and agitation, and label the vial with the reconstitution date and concentration. Discard any solution that turns cloudy or shows particulates.
Degradation rates differ by sequence: peptides containing methionine, cysteine, asparagine or glutamine are more prone to oxidation and deamidation, so shelf life after reconstitution is compound-specific rather than universal.
Read the full guide: how to store peptides before and after reconstitution →
Source: Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544–575. (PMID 20143256). General guidance for research handling; not product-specific instructions.
PACAP-38: frequently asked questions
What is PACAP-38?
38-aa neuropeptide that activates PAC1/VPAC receptors. Research tool in migraine, neuroprotection, and metabolic models. Not FDA-approved as a drug.
How does PACAP-38 work?
Pituitary adenylate cyclase-activating polypeptide is a 38-amino-acid neuropeptide closely related to vasoactive intestinal peptide, sharing roughly two-thirds sequence identity. It binds the PAC1 receptor with high selectivity and also engages VPAC1 and VPAC2; all are Gs-coupled, so activation raises cyclic AMP in neurons and endocrine cells.
Is PACAP-38 FDA approved?
No. PACAP-38 is not approved by the FDA for any indication and is categorised as research-only. It has not been reviewed for safety or efficacy as a medicine, and published research should be read as investigation rather than established use.
What is the half-life of PACAP-38?
Reported half-life for PACAP-38 is Very short; rapidly degraded by peptidases. Half-life describes how long the compound persists in circulation, not how long any effect lasts, and published figures vary with route of administration, formulation and the population studied.
What peptides are similar to PACAP-38?
Compounds most often compared with PACAP-38 include 5-Amino-1MQ, Adamax, Adipotide and AICAR. They are grouped by shared mechanism or research area rather than by equivalence, and their regulatory status and evidence base differ.
References
- PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial — J Headache Pain, 2025External reference
- Part I: Pituitary adenylate cyclase-activating polypeptide-38 induced migraine-like attacks in patients with and without familial aggregation of migraine — Cephalalgia, 2017External reference
- PACAP-38 is increased in the tear fluid of patients with migraine — J Neurol Neurosurg Psychiatry, 2026External reference
- Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache — Brain, 2026External reference
- Pituitary adenylate cyclase-activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells — PLoS One, 2018External reference
Related research, comparisons & guides
Related peptides
Compiled by Peptide Library Editorial · Reviewed Aug 30, 2026 · Updated Nov 7, 2026 · Version 2
This PACAP-38 profile is compiled from published literature (5 cited studies linked above), public regulatory records and chemical registries. It describes what research reports; it is not medical advice, and nothing here is a dosing recommendation for humans. Peptide Library does not sell peptides. Editorial policy · How profiles are compiled · Report an error
Track PACAP-38 research, inventory and reconstitution in the free Peptide Library app. Get the app for iOS or Android →