PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide)

Also known as: PACAP-38, PACAP-27, ADCYAP1

NeuroprotectiveCognitive & Nootropic

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

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

No established human therapeutic dosing. Research doses: 1-10 nmol intranasally or IV in animal models.

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

Synergistic Compounds

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

VIPBDNFNGF

Learn More

Beginner's GuideNew to peptides? Start hereStacking GuideSynergistic combinationsAdministration RoutesSubQ, IM, oral, nasal & moreReconstitution CalculatorCalculate exact dosingPeptides vs SARMsFull comparisonHow Peptides Are MadeSPPS, purification & QC

References & Further Reading

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