Vasoactive Intestinal Peptide
Also known as: VIP, Aviptadil (synthetic form, RLF-100), PHM-27 (related peptide, peptide histidine methionine), Vasoactive Intestinal Polypeptide, Pemziviptadil / PB1046 (long-acting VIP analogue), IK312548 (stable VIP derivative)
Endogenous neuropeptide / neuroendocrine peptide — member of the secretin/glucagon superfamily; vasodilator, bronchodilator, and immunomodulatory agent
What it is
Used in research and clinical trials for severe lung conditions, autoimmune diseases, and pulmonary arterial hypertension, VIP is a natural peptide the body produces to open airways, relax blood vessels, and calm immune overreactions. Its synthetic form, aviptadil, has been tested in COVID-19 respiratory failure and rare lung disease.
The scientific side
vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide belonging to the secretin/glucagon superfamily, originally isolated from porcine duodenum and subsequently found throughout the central and peripheral nervous systems, immune cells, pulmonary tissue, and endocrine organs. VIP mediates its effects by binding primarily to VPAC1 (VIP receptor 1) and VPAC2 (VIP receptor 2) — G protein-coupled receptors that activate adenylyl cyclase, raising intracellular cyclic AMP (cAMP) — as well as CRTH2 and PAC1 receptors on immune and neural cells. In pulmonary biology, VIP acts as a potent bronchodilator and pulmonary vasodilator through the inhibitory non-adrenergic, non-cholinergic (iNANC) airway nervous system; in idiopathic pulmonary arterial hypertension (PAH), VIP is found to be deficient in lung tissue, suggesting a physiological role in maintaining normal pulmonary vascular tone. Inhaled aviptadil (synthetic VIP) caused selective acute pulmonary vasodilation in a study of 20 PAH patients undergoing right-heart catheterization, improving stroke volume and mixed venous oxygen saturation without systemic hypotension. In the immune system, VIP inhibits pro-inflammatory cytokine synthesis — including IL-6 — shifts macrophage polarization toward anti-inflammatory (M2) phenotypes, promotes regulatory T cell expansion, and suppresses TH1-driven autoimmune responses. In COVID-19 respiratory failure, VIP/aviptadil was hypothesized to upregulate surfactant production, block SARS-CoV-2 cytopathy in type II alveolar cells, and inhibit cytokine storm — mechanisms supported by nonclinical data but ultimately not translated into statistically significant benefit in the large Phase III TESICO RCT. In type 2 diabetes models, VIP stimulates glucose-dependent insulin secretion via VPAC2 receptor signaling in pancreatic beta cells and promotes beta-cell proliferation through the forkhead box M1 (FoxM1) pathway. In autoimmune disease, VIP regulates the PTEN/PI3K/AKT signaling axis, shifts the Treg/Th17 balance, and reduces inflammatory cytokine expression in models of Sjogren's disease and rheumatoid arthritis. A principal pharmacological limitation is VIP's extremely short plasma half-life (approximately 1–2 minutes), driven by rapid enzymatic degradation — a key driver of research into stable analogues, nanoparticle delivery systems, and long-acting conjugates such as pemziviptadil (PB1046).
Class: Endogenous neuropeptide / neuroendocrine peptide — member of the secretin/glucagon superfamily; vasodilator, bronchodilator, and immunomodulatory agent
Legal & regulatory status
Not FDA-approved as a standalone therapeutic. VIP itself is an endogenous peptide used as a research tool. Aviptadil (synthetic VIP, RLF-100), developed by NeuroRx/Relief Therapeutics, received FDA Breakthrough Therapy…
Vasoactive intestinal peptide (VIP) and synthetic analogues such as aviptadil are not explicitly listed by name on the WADA Prohibited List as of the reviewed literature period. However, VIP and its analogues have…
VIP (vasoactive intestinal peptide) and aviptadil are not approved by Health Canada as marketed therapeutic products. Aviptadil was not submitted for or granted Notice of Compliance (NOC) approval in Canada as of…
What it's studied for
- Acute COVID-19 respiratory failure / ARDS — intravenous aviptadil (synthetic VIP) Phase III RCT
- Pulmonary arterial hypertension (PAH) — inhaled aviptadil as pulmonary vasodilator Human observational
- Chronic obstructive pulmonary disease (COPD) and asthma — inhaled VIP analogues as bronchodilator/anti-inflammatory Mixed
- Autoimmune/inflammatory conditions — rheumatoid arthritis and Sjogren's disease Mixed
- Type 2 diabetes — VPAC2 receptor agonism for glucose-dependent insulin secretion Mechanistic only
- Migraine and headache — vascular and trigeminovascular mechanisms Human observational
- VIPoma — diagnosis and endocrine tumor management Human observational
Safety signals
- Systemic hypotension and flushing from vasodilatory effects
- Failure to demonstrate efficacy in Phase III COVID-19 respiratory failure (TESICO trial stopped for futility)
- Adverse events in COVID-19 RCT — numerically higher composite serious adverse event rate with aviptadil than placebo
- Extremely short plasma half-life (approximately 1–2 minutes) with risk of unpredictable dosing in non-clinical settings
- Pro-diarrheal and secretomotor effects — risk of watery diarrhea with excess VIP (VIPoma model)
- Cardiovascular effects — tachycardia, increased heart rate, and cardiac contractility changes
- Theoretical risk of promoting tumor growth in VIP-receptor-overexpressing cancers
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Intravenous infusion | 600 pmol/kg (Day 1), 1200 pmol/kg (Day 2), 1800 pmol/kg (Day 3) | — | Adults with COVID-19 acute hypoxaemic respiratory failure — TESICO Phase III RCT | Research |
| Inhaled aerosol | 100 mcg single inhaled dose | — | Adults with chronic pulmonary hypertension — acute hemodynamic assessment | Research |
| Inhaled VIP | Not specified in reviewed abstract | — | Adults with severe COPD — NCT00464932 pilot clinical study | Research |
| Dry powder inhaler (DPI) | Not specified in abstract for human use; animal study doses used | — | Preclinical/stable analogue development for asthma/COPD — IK312548 dry powder inhaler | Research |
| Intranasal or subcutaneous injection reported anecdotally in research communities; IV administration was used in clinical trials | Not established; no consensus community dose documented in reviewed sources | Not established | Adults exploring VIP for immune modulation, MCAS (mast cell activation syndrome), or pulmonary support — off-label research context |
No peer-reviewed studies indexed for this peptide yet.