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CFPS Research Archives

Vasoactive Intestinal Peptide

Human clinical Immune Support 3 sources

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide that functions as a potent vasodilator, immune regulator, and neurotransmitter. Research highlights its ability to reduce inflammation, regulate immune responses, and improve respiratory and cardiovascular conditions.

01Dosing reference

Amount
50-100 mcg (nasal spray) or continuous IV infusion in clinical settings
Frequency
1-4 times daily (nasal spray)
Cycle
Ongoing based on symptom management or acute short-term use in critical care
Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

01

Receptor Binding

VIP binds to VPAC1 and VPAC2 receptors, which are G-protein coupled receptors found throughout the body, including the immune, respiratory, and central nervous systems.

02

cAMP Activation

Binding activates the adenylate cyclase pathway, increasing intracellular cAMP levels, which leads to smooth muscle relaxation and modulation of cytokine production.

03

Anti-inflammatory & Vasodilatory Effects

This results in vasodilation, bronchodilation, and a shift in the immune response from pro-inflammatory to anti-inflammatory, offering potential benefits for respiratory failure and autoimmune conditions.

03Human evidence

Intravenous VIP (Aviptadil) improved outcomes in patients with critical COVID-19 respiratory failure.

A 60-day randomized clinical trial showed improved survival and recovery from respiratory failure in critically ill patients.

VIP infusion can trigger migraine-like headaches in susceptible individuals.

A randomized clinical trial demonstrated that VIP infusion caused delayed headaches and cranial hemodynamic changes in healthy volunteers and migraine patients.

04Preclinical evidence

VIP acts as a potent anti-inflammatory factor by regulating cytokine production.

In vitro and animal models of autoimmune diseases showed VIP reduces pro-inflammatory mediators and increases anti-inflammatory cytokines.

VIP promotes neuronal survival and exhibits neuroprotective properties.

Animal models demonstrated that VIP and its lipophilic analogs protect neurons from various toxic insults, partly through cAMP-independent mechanisms.

05What is known vs. unknown

Reasonably established
  • VIP is a naturally occurring 28-amino acid neuropeptide with widespread distribution in the human body.
  • It acts as a potent vasodilator and bronchodilator, relaxing smooth muscles in blood vessels and airways.
  • VIP has significant immunomodulatory effects, generally suppressing pro-inflammatory responses.
  • Clinical formulations of VIP (like Aviptadil) have been investigated for severe respiratory conditions and pulmonary hypertension.
Unknowns & limits
  • The short half-life of natural VIP in circulation limits its therapeutic utility without continuous infusion or modified analogs.
  • The exact mechanisms by which VIP triggers headaches in certain individuals remain under investigation.
  • Long-term safety and efficacy of VIP agonists for chronic inflammatory or autoimmune conditions are not fully established in humans.

06Safety & regulatory context

Regulatory statusVIP is generally well-tolerated when administered in controlled clinical settings, but it can cause side effects such as flushing, hypotension (low blood pressure), tachycardia, and headaches. In some individuals, particularly those prone to migraines, VIP infusion can trigger severe headaches. Formulations of VIP, such as Aviptadil, have been investigated in clinical trials for conditions like acute respiratory distress syndrome (ARDS) and pulmonary hypertension, and have received emergency use authorizations or orphan drug designations in specific contexts, but it is not broadly FDA-approved for general use or anti-aging purposes.

07Compared with PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide)

Vasoactive Intestinal Peptide vs. PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide)
Key difference
While both bind to VPAC1 and VPAC2 receptors, PACAP also binds with high affinity to the PAC1 receptor, giving it distinct neuroprotective and endocrine functions compared to VIP's primary vasodilatory and immune roles.
When researchers discuss each
VIP is typically discussed in the context of immune regulation, respiratory conditions, and vasodilation, whereas PACAP is often highlighted for its neuroprotective and stress-response mechanisms.

08Glossary

Vasodilation
The widening of blood vessels, which decreases blood pressure and increases blood flow.
Neuropeptide
Small protein-like molecules used by neurons to communicate with each other.
Secretagogue
A substance that causes another substance to be secreted, such as VIP stimulating digestive secretions.
cAMP
Cyclic adenosine monophosphate, a secondary messenger important in many biological processes, including smooth muscle relaxation.

09Knowledge check

Q1Which receptors does Vasoactive Intestinal Peptide (VIP) primarily bind to?
Q2What is a common physiological effect of VIP administration?
Q3Which documented limitation of natural VIP most directly explains why therapeutic use often requires continuous infusion or modified analogs?
Q4According to the dossier's comparison with PACAP, which statement best captures a key difference between VIP and PACAP?
Q5Which statement about the clinical and regulatory status of VIP formulations (for example, Aviptadil) is supported by the dossier?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.