# VIP

> Evidence tier A — Controlled human trials · Mind · reviewed 2026-11-08
> Source page: https://peptidemeta.com/p/vip/

Also known as: Aviptadil, Vasoactive intestinal polypeptide, RLF-100, Zyesami

## Quick answers

**What is VIP?**

Vasoactive intestinal peptide is a 28-amino-acid neuropeptide involved in circadian rhythm regulation, immune modulation, and smooth-muscle relaxation.

**How strong is the evidence for VIP?**

Tier A (controlled human trials) on the peptidemeta evidence scale. Randomized placebo-controlled trials of aviptadil exist (erectile dysfunction with phentolamine, 1999; COVID-19 respiratory failure, TESICO 2023); nationally authorised in some European countries but not FDA- or centrally EMA-approved.

**Is VIP FDA-approved?**

No. VIP is not approved by the FDA for any use. Intravenous aviptadil (RLF-100/Zyesami) was studied for COVID-19 respiratory failure but not approved. Outside the US: Invicorp (aviptadil + phentolamine) for erectile dysfunction — nationally authorised in several European countries; first approval Denmark (1998).

**Is VIP banned in sport?**

No. VIP is not on the World Anti-Doping Agency Prohibited List.

**How does VIP work?**

VIP binds VPAC1 and VPAC2 G-protein-coupled receptors, activating adenylyl cyclase and increasing intracellular cAMP. In immune cells this suppresses pro-inflammatory cytokine production (TNF-alpha, IL-6) and promotes regulatory T-cell differentiation.

**What is known about the safety of VIP?**

Endogenous neuropeptide with established physiology. Intranasal use in CIRS protocols comes from uncontrolled clinical reports.

## Key facts

- **Evidence tier:** A (Controlled human trials)
- **FDA:** not approved
- **Other approvals:** Invicorp (aviptadil + phentolamine) for erectile dysfunction — nationally authorised in several European countries; first approval Denmark (1998)
- **WADA:** not on the Prohibited List
- **Peptide:** yes
- **Sequence:** HSDAVFTDNYTRLRKQMAVKKYLNSILN[NH2] (28 residues)
- **Formula:** C147H238N44O42S
- **Molecular weight:** 3325.8 g/mol
- **Discovered:** 1970 — Isolated from porcine small intestine by Said and Mutt (Science 1970).
- **Routes studied:** Intranasal, Subcutaneous

## Overview

Vasoactive intestinal peptide is a 28-amino-acid neuropeptide involved in circadian rhythm regulation, immune modulation, and smooth-muscle relaxation. As aviptadil it has been tested in randomized trials, and intranasal VIP is used in some chronic inflammatory response syndrome (CIRS) protocols without controlled-trial support.

## Mechanism

VIP binds VPAC1 and VPAC2 G-protein-coupled receptors, activating adenylyl cyclase and increasing intracellular cAMP. In immune cells this suppresses pro-inflammatory cytokine production (TNF-alpha, IL-6) and promotes regulatory T-cell differentiation. In the brain it serves as a key circadian clock synchronizer in the suprachiasmatic nucleus.

## Effects reported in research

_Reported outcomes, not promises; see the evidence tier._

- Regulation of circadian rhythms
- Anti-inflammatory immune modulation
- Vasodilation and smooth-muscle relaxation
- Pulmonary vasodilation (small open-label pulmonary hypertension studies)

## Safety & unknowns

Endogenous neuropeptide with established physiology. Intranasal use in CIRS protocols comes from uncontrolled clinical reports. Side effects may include nasal irritation, transient diarrhea, and hypotension. Not FDA-approved for any indication; aviptadil with phentolamine (Invicorp) is nationally authorised for erectile dysfunction in some European countries.

## Studies

- Brown SM, Barkauskas CE, Grund B, et al. (2023). *Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial*. The Lancet Respiratory Medicine. Clinical trial. https://pubmed.ncbi.nlm.nih.gov/37348524/
  In 461 patients with COVID-19-associated acute hypoxaemic respiratory failure, intravenous aviptadil did not significantly improve clinical outcomes at day 90 compared with placebo.

## Status sources

- [KEGG DRUG D12127 — aviptadil (sequence, formula, MW)](https://www.kegg.jp/entry/D12127)
- [EMA — nationally authorised products: aviptadil/phentolamine](https://www.ema.europa.eu/en/documents/psusa/aviptadil-phentolamine-mesilate-list-nationally-authorised-medicinal-products-psusa00010814202202_en.pdf)
- [Dinsmore et al., BJU Int 1999 (ED RCT)](https://pubmed.ncbi.nlm.nih.gov/10233493/)
- [TESICO, Lancet Respir Med 2023 (COVID-19 RCT)](https://pubmed.ncbi.nlm.nih.gov/37348524/)
- [Said & Mutt, Science 1970 (isolation)](https://pubmed.ncbi.nlm.nih.gov/5450698/)

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Educational reference only — not medical advice. No dosing information is published. Tiers rate the strength of published evidence, not effectiveness or safety.