PACAP-38
preclinicalAlso known as: Pituitary adenylate cyclase-activating polypeptide
**Mechanism of Action** PACAP-38 (pituitary adenylate cyclase-activating polypeptide) is a 38-amino-acid neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin family. It exerts its effects primarily through high-affinity binding to the PAC1 receptor, a G-protein-coupled receptor that activates adenylate cyclase, increasing intracellular cAMP levels. This signaling cascade mediates neuroprotective, anti-apoptotic, and vasoregulatory functions, including modulation of cerebral blood flow, suppression of neuroinflammation, and stabilization of the blood-brain barrier. PACAP-38 also interacts with VPAC1 and VPAC2 receptors, though with lower affinity, contributing to its pleiotropic effects in the central and peripheral nervous systems. **Key Research Findings** Preclinical studies (PubMed: 3103 references) demonstrate PACAP-38’s neuroprotective efficacy in models of ischemic stroke, traumatic brain injury, and neurodegenerative diseases such as Parkinson’s and Alzheimer’s. It reduces infarct volume, attenuates oxidative stress, and promotes neuronal survival via cAMP/PKA and MAPK/ERK pathways. Additionally, PACAP-38 exhibits vasodilatory properties in cerebral and peripheral arteries, with evidence of improved microcirculation in models of subarachnoid hemorrhage. However, its short plasma half-life and limited blood-brain barrier penetration remain translational challenges. **Clinical Relevance** PACAP-38 is in preclinical development, with no approved clinical applications. Its potential lies in acute neuroprotection (e.g., stroke, traumatic brain injury) and chronic neurodegenerative conditions, though pharmacokinetic optimization (e.g., analogs, intranasal delivery) is required. The peptide’s role in migraine pathophysiology (via PAC1 receptor antagonism) is also under investigation, but therapeutic use remains experimental. For research purposes only — not medical advice.
Key data
C203H331N63O53SResearch & studies
PACAP infusions can provoke migraine attacks in patients.; A monoclonal antibody against the PACAP receptor failed in a placebo-controlled study.; Lu AG09222 (anti-PACAP antibody) reduced monthly migraine days vs placebo in a small proof-of-concept study.; The PROCEED study is testing four doses of Lu AG09222 for migraine prevention, with results expected in 2025.
PACAP improves stroke outcomes and dementia in animal models.; PACAP can cross the blood-brain barrier, aiding in therapy for neurodegenerative diseases.; PACAP may serve as a potential drug for treatment, prevention, or management of stroke and Alzheimer's disease.
Frequently asked questions
What is PACAP-38?
**Mechanism of Action** PACAP-38 (pituitary adenylate cyclase-activating polypeptide) is a 38-amino-acid neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin family. It exerts its effects primarily through high-affinity binding to the PAC1 receptor, a G-protein-coupled receptor that activates aden
How does PACAP-38 work?
38-aa neuropeptide of the VIP/secretin family acting on PAC1 receptors; neuroprotective and vasoregulatory.
What is the research status of PACAP-38?
PACAP-38 is currently classified as preclinical, with 3,103 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of PACAP-38?
PACAP-38 has a molecular weight of approximately 4534 g/mol (formula C203H331N63O53S).
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