VIP
Vasoactive intestinal peptide studied for immune and gut modulation.
- Status
- Research / not approved
- Developer
- Endogenous neuropeptide (Said & Mutt, 1970); synthetic aviptadil (RLF-100) by NeuroRx / Relief Therapeutics
- Receptors / target
- VPAC1 and VPAC2 receptors (class-B Gs-coupled GPCRs) -> cAMP; vasodilatory, anti-inflammatory and pulmonary signaling
- FDA-approved?
- NO
- Prescription available?
- NO
- Studied for
- acute respiratory failure / ARDS (investigational)pulmonary hypertensionerectile dysfunction (Invicorp, with phentolamine)sarcoidosis / inflammation
Overview
VIP (vasoactive intestinal peptide) is a 28-amino-acid neuropeptide with broad vasodilatory, anti-inflammatory and pulmonary actions. The synthetic form, aviptadil (RLF-100), is investigational. It is best known recently for COVID-19 respiratory-failure trials, and the aviptadil+phentolamine combination (Invicorp) is approved in some countries for erectile dysfunction. It is not FDA-approved in the US, and the popular intranasal "CIRS/mold" use is not evidence-based. Sold research-only here.
Mechanism
VIP signals through the class-B G-protein-coupled receptors VPAC1 and VPAC2, raising intracellular cAMP. Downstream effects include smooth-muscle relaxation/vasodilation (notably pulmonary and cavernosal), bronchodilation, and broad anti-inflammatory/immunomodulatory signaling. Its very short plasma half-life (minutes) limits systemic dosing and motivated inhaled/intravenous formulations of aviptadil.
Clinical evidence
Human evidence is mixed and, for the headline use, negative. The large NIH TESICO RCT (Lancet Respiratory Medicine 2023) found intravenous aviptadil did not improve outcomes in COVID-19 hypoxaemic respiratory failure and was stopped for futility — contradicting earlier favorable company press releases. For erectile dysfunction, the aviptadil+phentolamine product (Invicorp) is genuinely effective and approved in several countries (not the US). An early pulmonary-hypertension pilot suggested benefit, but later work was unconvincing. Receptor pharmacology is well characterized (IUPHAR review).
Safety profile
VIP/aviptadil's expected effects follow its vasodilatory pharmacology: hypotension, flushing and diarrhea, plus injection-site reactions. In the controlled respiratory trials it was generally tolerated, but without an efficacy benefit. There is no established long-term safety profile for chronic or intranasal self-administration, and the molecule is not FDA-approved in the US. It is not on the WADA list. Research-use only — nothing here is treatment or dosing guidance, and the intranasal "mold-illness" use lacks controlled evidence.
- During infusion (acute)
Very short half-life (~minutes); given by IV infusion in trials. Acute hemodynamic effects (vasodilation, flushing, hypotension) can occur.
- Trial outcomes
The rigorous COVID-19 ARDS RCT (TESICO) was negative; the intranasal 'CIRS/mold' use is not evidence-based. No established benefit time-course.
Reported in published literature and user reports. Not a complete list, and not medical advice.
- Hypotension
- Facial flushing
- Diarrhea
- Injection-site reactions
If severe or unexpected symptoms occur, contact a qualified medical professional. PEPTIDES·INDEX does not provide medical advice.
- No FDA-approved US label exists; the following follow from its vasodilatory pharmacology and are precautionary.
- Hypotension or hemodynamic instability, given VIP's blood-pressure-lowering vasodilation
- Known hypersensitivity to aviptadil or formulation components
- Pregnancy and breastfeeding: human safety data are absent
- Antihypertensive and other vasodilator drugsPotential additive hypotension (mechanism-based caution; not formally characterized in humans, research use only)
Compare
- vs ARA-290
Both are investigational, short-half-life peptides with anti-inflammatory rationale, but ARA-290 targets the innate repair receptor for neuropathy with positive phase 2 trials, whereas VIP/aviptadil targets VPAC vasodilatory/pulmonary signaling and its headline COVID-ARDS trial was negative.
FAQ
Is VIP (aviptadil) FDA-approved?
No. Aviptadil (RLF-100), the synthetic form of VIP, is investigational and not FDA-approved in the US. The aviptadil+phentolamine combination (Invicorp) is approved in some countries for erectile dysfunction, but not in the US. Sold research-use only.
Did VIP work for COVID-19 respiratory failure?
No. The large NIH TESICO randomized trial (Lancet Respiratory Medicine, 2023) found intravenous aviptadil did not improve outcomes in COVID-19 hypoxaemic respiratory failure and was stopped for futility, contradicting earlier favorable company press releases.
Is the intranasal mold-illness (CIRS) use evidence-based?
No. The popular intranasal VIP protocol for CIRS/mold illness is not supported by controlled trials. There is no established long-term safety profile for chronic or intranasal self-administration.
What are the main side effects of VIP/aviptadil?
Its effects follow its vasodilatory pharmacology: hypotension, facial flushing and diarrhea, plus injection-site reactions. Because of the blood-pressure-lowering effect, additive hypotension is a mechanism-based concern when combined with antihypertensive or other vasodilator drugs. Caution is warranted in hypotension or hemodynamic instability.
Why does VIP have such a short half-life?
VIP is a 28-amino-acid neuropeptide rapidly degraded by peptidases, giving a plasma half-life of only about one to two minutes. That short window limits practical systemic dosing and is why aviptadil has been formulated for intravenous infusion and inhaled/intranasal delivery rather than simple injection.
Is VIP useful for erectile dysfunction?
Yes, in a specific approved combination outside the US. The aviptadil-plus-phentolamine product Invicorp is approved in several countries as an intracavernosal injection for erectile dysfunction, exploiting VIP's vasodilatory action. It is not FDA-approved in the US, and this is regulatory context, not medical advice.
Similar compounds
Starting references for the library summary. These are not dosing instructions or medical advice.
For research-use educational context only. Not medical advice and not a recommendation to use any compound. Consult a qualified healthcare professional before any health decision.