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Hormonal & reproductive

Vasoactive intestinal peptide (VIP)

Also called VIP, aviptadil, Zyesami, RLF-100

VIP is a natural hormone and brain signaling peptide that relaxes blood vessels and smooth muscle and calms inflammation. A synthetic version, aviptadil, was tested as an IV treatment for critical COVID-19, but the FDA twice declined emergency authorization and a large NIH trial stopped the arm for lack of benefit. Compounded VIP is used by some clinics, and FDA lists it as under evaluation.

Late-stage trialsTested in large human trials (phase 2b/3) but not yet approved in the US.

All printable flashcards

Drawn from its published sequence: 28 residues, one bead each.

Overview

VIP is a natural hormone and brain signaling peptide that relaxes blood vessels and smooth muscle and calms inflammation. A synthetic version, aviptadil, was tested as an IV treatment for critical COVID-19, but the FDA twice declined emergency authorization and a large NIH trial stopped the arm for lack of benefit. Compounded VIP is used by some clinics, and FDA lists it as under evaluation.

How it works

Established in physiology: VIP binds VPAC1 and VPAC2 receptors, relaxing smooth muscle and blood vessels and dampening inflammation. Proposed therapeutic uses (lung injury, inflammatory conditions) rely on these effects but have not been proven in large trials.

What research shows

  • NIH ACTIV-3b: aviptadil arm stopped in May 2022 at an interim analysis for failing to beat placebo in critical COVID-19 1.
  • NRx's narrower second EUA request relied on a post hoc subgroup analysis; FDA declined it 1.

Doses studied in people

Doses from COVID-19 trials were not verified in this review; no FDA-approved VIP product exists in the US.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

VialLiquid addedConcentrationPer unit (0.01 mL)
5 mg1 mL5 mg/mL50 mcgOpen in calculator
5 mg2 mL2.5 mg/mL25 mcgOpen in calculator
5 mg3 mL1.67 mg/mL16.7 mcgOpen in calculator
10 mg1 mL10 mg/mL100 mcgOpen in calculator
10 mg2 mL5 mg/mL50 mcgOpen in calculator
10 mg3 mL3.33 mg/mL33.3 mcgOpen in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

  • Long-term safety of compounded VIP is unknown.
  • FDA has not completed its evaluation of VIP for compounding 2.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

History

Discovered in the early 1970s. NRx/NeuroRx developed IV aviptadil (Zyesami, RLF-100) for COVID-19 respiratory failure. The NIH ACTIV-3b trial stopped its aviptadil arm in May 2022 after it failed to beat placebo, and FDA declined an emergency use authorization twice, the second time on July 1, 2022.

Common questions

Is VIP or aviptadil FDA-approved?

No. FDA twice declined emergency authorization for aviptadil in COVID-19, the second time on July 1, 2022 1.

Did aviptadil help in COVID-19?

The NIH ACTIV-3b trial stopped its aviptadil arm in May 2022 because it did not beat placebo in critical COVID-19 1. A later, narrower request leaned on an after-the-fact subgroup analysis, and FDA declined it 1.

Can VIP be compounded in the US?

VIP is in Category 1 (under evaluation) on FDA's May 14, 2026 list, so it may be compounded under FDA's interim enforcement discretion while the review continues 2.

Is VIP safe?

Long-term safety of compounded VIP is unknown, and FDA has not finished its evaluation of VIP for compounding 2.

Is VIP banned in sport?

It is not named on WADA's 2026 Prohibited List 3.

Related compounds

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Oxytocin

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Oxytocin is a natural hormone made in the brain that triggers labor contractions and milk let-down, and it also plays a role in social bonding.

Sources

  1. Fierce Biotech: Déjà vu: FDA rejects NRx filing for emergency use in COVID-19 (July 1, 2022) Regulatory
  2. FDA: Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (updated May 14, 2026) Regulatory
  3. WADA 2026 Prohibited List (official English text, Dutch Treaty Series Trb. 2026, 25) Regulatory

Last reviewed 2026-10-25 · How we research · Found an error? See our corrections policy.