VIP

Origin and structure

VIP was isolated in 1970 by Sami Said and Viktor Mutt from pig small intestine. The peptide they described widened blood vessels, lowered blood pressure, increased cardiac output and stimulated breathing, which is where the name comes from. It is a chain of 28 amino acids, HSDAVFTDNYTRLRKQMAVKKYLNSILN, ending in an amidated asparagine.

In the body VIP works mostly as a local messenger: nerve fibres release it close to their target in the gut wall, the airways, blood vessels and the genitals, and immune cells make it too. Aviptadil is the international drug name for synthetic VIP and is chemically identical to the natural peptide. It has been developed in two very different directions: Invicorp, which combines it with phentolamine as an injection for erectile dysfunction, and Zyesami, the intravenous form NRx Pharmaceuticals tested in critical COVID-19.

How it works

VIP binds two receptors, VPAC1 and VPAC2, which it shares with the closely related peptide PACAP. Both raise cyclic AMP inside the cell, and the most consistent result is relaxation of smooth muscle: blood vessels widen, airways open and the erectile tissue of the penis relaxes. Given into a vein it causes flushing, a faster heart rate and a fall in blood pressure, and it makes the gut secrete water, which is why diarrhoea shows up in infusion trials. In Invicorp it is paired with phentolamine, an alpha-blocker that widens the penile arteries.

In animal models of chronic inflammation VIP damps inflammatory signalling and pushes T cells towards a regulatory type. The only human test of that idea is a 2010 open-label study in 20 people with active sarcoidosis: four weeks of inhaled VIP lowered production of the inflammatory messenger TNF-alpha by cells washed out of the lungs and raised the number of regulatory T cells. It was small and had no placebo group.

Is VIP approved?

Only as part of a combination. Invicorp, an injection into the penis containing 25 micrograms of aviptadil and 2 mg of phentolamine mesilate, is authorised for erectile dysfunction in several European countries through national and decentralised procedures rather than through the EMA. The EMA's list of these national authorisations (October 2022) names Germany, Denmark, Finland, France, Norway and Sweden, plus Northern Ireland, all held by the Swedish company Evolan Pharma; the Netherlands is not on it. VIP on its own is not an authorised medicine in the EU, and no medicine has been approved for the uses VIP is sold for online, such as immune, gut or mould-related complaints.

In the Netherlands VIP on its own is not a registered medicine and may not be sold or promoted for human use; Invicorp was not authorised here either at the time of the EMA's 2022 list. VIP is available as research material, which is the basis our shop operates on.

In the United States no product containing aviptadil is approved. NRx Pharmaceuticals asked the FDA for emergency use authorisation of intravenous aviptadil (Zyesami) in critical COVID-19; the FDA declined in November 2021 and again on 1 July 2022, the second time for a narrower group of patients picked out by a post-hoc subgroup analysis. VIP sits in Category 1 of the FDA's list of bulk substances nominated for pharmacy compounding, the group still under evaluation, and was still there in the list updated on 14 May 2026. The FDA's interim policy does not stop pharmacies compounding with Category 1 substances while that review continues, but this is not an approval.

In sport, neither VIP nor aviptadil is named on the 2026 WADA Prohibited List. Class S0 covers substances with no current approval for human use by any regulator, and aviptadil has one, in Invicorp.

What the research shows

VIP has been tested in people for three main purposes: erectile dysfunction, lung disease (above all COVID-19) and a mould-related illness called CIRS. Only the first led to a licensed medicine. The main studies:

• Erectile dysfunction (BJU International 1999): 236 men at eight clinics. In the placebo-controlled phase, 171 men self-injected up to 12 times over six months; 75% responded to VIP with 1 mg phentolamine against 12% on placebo, and 66% to VIP with 2 mg phentolamine against 18%. Flushing followed 40% of 1,711 injections, and there was one episode of priapism.
• NRx trial in COVID-19 (Critical Care Medicine 2022): 196 critically ill patients at ten US hospitals, randomised 2:1 to three days of intravenous aviptadil or placebo. The primary endpoint, alive and free of respiratory failure at day 60, was missed (odds ratio 1.6, 95% CI 0.86 to 3.11); in this company-sponsored trial the authors emphasised a survival difference in a secondary analysis.
• TESICO (Lancet Respiratory Medicine 2023): NIH-funded, 461 patients with COVID-19 respiratory failure at 28 US sites, 94% of them in intensive care. Aviptadil did not improve recovery at day 90 (odds ratio 1.11, 95% CI 0.80 to 1.55), 38% died against 36% on placebo (hazard ratio 1.04), and on 25 May 2022 the independent data and safety monitoring board recommended stopping the aviptadil comparison for futility.
• CIRS (Health 2013): 20 patients from Ritchie Shoemaker's clinic self-administered 50 micrograms of VIP by nasal spray four times a day for at least 18 months. The authors reported fewer symptoms and normalised blood markers, but the study was open-label with no control group, and the placebo-controlled trial announced in the paper has not been published.
• Migraine provocation (JAMA Network Open 2021): in 21 people with migraine, a two-hour VIP infusion triggered a migraine attack in 15 (71%) against 1 (5%) after placebo.

Side effects and warnings

VIP's side effects follow from what it does to blood vessels and the gut. In the NRx COVID-19 trial, mild to moderate diarrhoea affected 32.8% of patients on intravenous aviptadil against 1.5% on placebo; low blood pressure was common in both groups (26.0% against 21.5%), as it often is in intensive care. In people with migraine, an infusion triggered attacks in most of them.

For Invicorp, the product information says about 10% of patients have side effects. Flushing is common; headache, dizziness, palpitations and a fast heart rate are uncommon; priapism and nodules or scarring in the penis after repeated injections are rare; angina and heart attack are very rare. The label excludes men prone to priapism, for example with sickle-cell disease, and men with penile deformities or implants.

The routes used in the community guides, nasal spray and injection under the skin, have no controlled safety data. The CIRS study reported no dropouts because of side effects among its 20 patients over 18 months, which is far too small to rule out uncommon harms.

Frequently asked questions

Is VIP the same as aviptadil?

Chemically, yes. Aviptadil is the drug name for synthetic VIP with the natural 28-amino-acid sequence. Invicorp and Zyesami are product names: Invicorp combines aviptadil with phentolamine as an injection for erectile dysfunction, and Zyesami was the intravenous form tested in COVID-19.

Is VIP legal in the Netherlands?

VIP on its own is not a registered medicine and may not be sold or promoted for human use; the ED combination Invicorp was not authorised in the Netherlands either at the time of the EMA's 2022 list. VIP can be bought and sold as research material, which is the basis for our shop. Our guide on research-use-only products in the Netherlands explains what that status means.

Did aviptadil work against COVID-19?

No. The company's own trial of 196 patients missed its primary endpoint, and the independent NIH-funded TESICO trial of 461 patients found no benefit on recovery or survival and was stopped for futility. The FDA declined emergency use authorisation twice.

Does VIP nasal spray help with CIRS or mould illness?

That has not been shown. The evidence is one open-label study of 20 patients from a single clinic, without a control group, in which everyone knew they were receiving VIP. Improvements in such a design can come from time, earlier treatment steps or expectation, and no placebo-controlled trial has been published.

Is VIP banned in sport?

VIP is not named on the 2026 WADA Prohibited List. The catch-all class S0 covers substances with no current approval for human use by any regulator, and aviptadil has one, as part of Invicorp. Athletes in the Netherlands who are unsure about a substance can put the question to the Dopingautoriteit.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.