PACAP38

Summary

PACAP38 (Pituitary Adenylate Cyclase-Activating Polypeptide-38) is a 38-amino acid neuropeptide belonging to the secretin/glucagon/VIP superfamily. It is highly conserved across species and is widely expressed in the central and peripheral nervous systems. PACAP38 has potent neuroprotective, anti-inflammatory, vasodilatory, and neurotrophic properties. It is under investigation for migraine pathophysiology, neurodegenerative diseases, PTSD, and inflammatory conditions.

Mechanism of Action

Activates PAC1, VPAC1, and VPAC2 G-protein-coupled receptors, stimulating adenylyl cyclase and phospholipase C signaling cascades. Promotes cAMP and IP3/DAG second messenger production, leading to vasodilation, neurotrophic effects, neuroprotection, and modulation of neurotransmitter release.

Routes of Administration

Goals & Uses

• NeuroprotectionNeurologyModerate
• CardioprotectionCardiovascularLow
• PTSD and stress modulationPsychiatry / ResearchModerate
• Migraine research and provocation modelNeurologyHigh
• Anti-inflammatory effectsInflammationModerate

Contraindications

• Severe hypotension or cardiovascular instabilityCardiovascularHigh
• Known hypersensitivity to PACAP38 or related peptidesAllergyHigh
• Active migraine or severe headache disorder (provocative dosing)NeurologyModerate

Adverse Effects

• Facial flushingCardiovascular/DermatologicCommon
• HypotensionCardiovascularCommonLow blood pressure
• TachycardiaCardiovascularUncommonAbnormally fast heart rate
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Headache / migraine-like attackNeurologicalCommon

Drug Interactions

• Triptans / ErgotaminesLow
• Antihypertensive agentsModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric populationsAgeRelative
• Patients with cardiovascular diseaseComorbidityRelative

Regulatory Status

• European UnionUnapprovedResearch use only; utilized in EMA-governed clinical migraine provocation studies.
• United StatesUnapprovedResearch use only; used in FDA-regulated clinical trials as investigational tool for migraine and CNS research.
• United KingdomUnapprovedResearch use only; no MHRA approval for clinical indications.

PACAP38 is not approved for clinical use by any major regulatory agency. It is used extensively as a research tool compound. Intravenous infusion of PACAP38 has been used in clinical studies to provoke migraine attacks, informing drug development targeting the PAC1 receptor pathway.

Evidence & Sources

No sources recorded yet.