Overview

PACAP is a 38-amino acid neuropeptide (with a shorter 27 AA form) belonging to the secretin/glucagon/VIP superfamily. It is one of the most potent known neuroprotective peptides, safeguarding neurons against ischemic, oxidative, and excitotoxic insults across multiple brain regions. PACAP plays important roles in neuronal differentiation, synaptic plasticity, and circadian rhythm regulation. Its diverse receptor profile and potent activity make it a significant research target for neurodegenerative diseases, traumatic brain injury, and PTSD.

Mechanism of Action

PACAP binds three receptors: PAC1 (ADCYAP1R1, high affinity, PACAP-selective) and VPAC1/VPAC2 (shared with VIP). PAC1 activation stimulates adenylyl cyclase (cAMP/PKA pathway) and phospholipase C (PKC pathway). These pathways activate MAPK/ERK, PI3K/Akt, and CREB-mediated gene expression, promoting expression of anti-apoptotic proteins (Bcl-2) and neurotrophic factors (BDNF, GDNF). PACAP also modulates voltage-gated calcium channels and inhibits caspase-3 activation.

Potential Benefits

  • Potent neuroprotection against ischemia and oxidative stress
  • Neuronal differentiation support
  • Synaptic plasticity and LTP enhancement
  • Circadian rhythm regulation
  • PTSD-related stress response modulation (PAC1 receptor)
  • Potential in TBI and neurodegenerative disease

Dosage Protocols

The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.

BeginnerNot a consumer research peptide
IntermediateN/A
AdvancedN/A
Cycle DurationN/A — research use

PACAP-38 or PACAP-27 used in research. Clinical development for migraine (antagonists) — not agonists.

Routes of Administration

Intravenous (research) 100%

Used in migraine provocation studies.

Intranasal (research) Moderate CNS delivery

Preclinical neuroprotection studies.

Stacking Protocols

Popular research stacks involving PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide):

Research Context Only

PACAP is a research tool. Migraine therapeutics target PACAP antagonists (e.g. Lundbeck's Lu AG09222).

Reconstitution

StorageRefrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution.

Typical vial sizes: 0.1-1 mg (research). Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.

Need exact syringe measurements?

Amino Acid Sequence

His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys-NH2

Side Effects & Safety

  • Vasodilation and hypotension at pharmacological doses
  • Nausea
  • Headache

Safety & Contraindications

This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.

Relative

Pregnancy / Lactation

Relative

Bleeding Disorders

Absolute

Active Skin Infection at Injection Site

Pharmacokinetics

Half-LifeNot well characterized for this peptide; consult primary literature
StorageStore lyophilized peptide at -20°C (long-term) or 2-8°C (short-term, under 30 days). Reconstituted: refrigerate at 2-8°C and use within 28-30 days. Protect from light. Do not freeze reconstituted solution.

Synergistic Compounds

The following compounds have been studied alongside PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) for potential complementary or synergistic effects:

VIPBDNFNGF

Learn More

References & Further Reading

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