VIP
Published research and evidence base
Vasoactive intestinal peptide is a 28-amino-acid neuropeptide that signals through the class B G protein-coupled receptors VPAC1 and VPAC2, with documented roles in pulmonary vasodilation, surfactant regulation, suppression of pro-inflammatory cytokine release, regulatory T cell induction, and synchronisation of circadian pacemaker neurons in the suprachiasmatic nucleus. Its synthetic form, aviptadil, has been tested in humans for COVID-19-associated acute hypoxaemic respiratory failure, sarcoidosis and erectile dysfunction. The largest randomised trial in respiratory failure (TESICO) found no significant clinical benefit for intravenous aviptadil versus placebo, and a 2025 systematic review of ARDS trials reported a pooled survival odds ratio of 1.01, while smaller inhaled-route and open-label studies reported favourable but non-definitive signals. An aviptadil-phentolamine intracavernosal combination is an established second-line agent in erectile dysfunction practice.
- Studies cited
- 15
- Published 2023+
- 9
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- VPAC1 and VPAC2 receptor pharmacology and cAMP signalling
- Aviptadil in ARDS and COVID-19 respiratory failure (largely negative randomised evidence)
- Pulmonary vasodilation and pulmonary arterial hypertension
- Immunomodulation, TNF-alpha suppression and regulatory T cell induction
- Circadian pacemaking and neuronal synchrony in the suprachiasmatic nucleus
- Inhaled delivery for chronic lung inflammation (sarcoidosis)
- Intracavernosal aviptadil-phentolamine for erectile dysfunction
- Short plasma half-life and the search for long-acting analogues
Compound identifiers
- CAS
- 40077-57-4
- PubChem
- 16132300
What VIP is, chemically.
- Molecular formula
- C147H237N43O43S
- Molecular weight
- 3326.8 g/mol
- CAS number
- 40077-57-4
- PubChem CID
- 16132300
invicorp
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
15 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Systematic review2025
Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis
Udupa AA, et al. · Indian Journal of Critical Care Medicine · systematic review and meta-analysis of 9 studies (2 randomised controlled trials, 7 case series), 665 patients of whom 361 received aviptadil, search to October 2025
Pooling the two randomised trials gave a survival odds ratio of 1.01 (95% CI 0.72-1.42, p=0.93), indicating no significant survival benefit for aviptadil over placebo in ARDS. Case series reported higher survival (88.9%) and improvements in oxygenation and inflammatory markers, but the authors noted these were uncontrolled.
- 02Human clinical2025
Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19
Esendagli D, et al. · Medical Principles and Practice · multicentre, prospective, double-blind, placebo-controlled randomised trial, 80 hospitalised adults with COVID-19 pneumonia across 9 centres
Mean time to discharge was 7.8 days with inhaled aviptadil versus 10.0 days with placebo (p=0.049), and improvement in CT lung damage score at day 28 was greater in the aviptadil arm (p=0.028). No dropouts occurred due to adverse effects; the trial was small and subsequently drew published methodological critiques.
- 03Human clinical2025
Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction
Al-Mitwalli A, et al. · The Journal of Sexual Medicine · retrospective single-centre cohort, 308 men with erectile dysfunction refractory to or intolerant of alprostadil, mean follow-up 13.3 months
Aviptadil-phentolamine intracavernosal injection was effective in 182 of 308 men (59%), with 76% efficacy among those switched for alprostadil-related pain versus 36% among alprostadil non-responders (p<0.0001). Facial flushing occurred in 22.5% and ischaemic priapism in one patient (0.3%).
- 04Human clinical2023
Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial
Brown SM, et al. · The Lancet Respiratory Medicine · randomised placebo-controlled trial (ACTIV-3b/TESICO), 461 adults in the modified intention-to-treat aviptadil comparison, 28 US sites
Intravenous aviptadil did not significantly improve clinical outcomes through day 90 compared with placebo; the odds ratio for a better category of the primary efficacy endpoint was 1.11 (95% CI 0.80-1.55, p=0.54). The authors concluded aviptadil showed no significant benefit in COVID-19-associated acute hypoxaemic respiratory failure.
- 05Human clinical2023
The effect of Lu AG09222 on PACAP38- and VIP-induced vasodilation, heart rate increase, and headache in healthy subjects: an interventional, randomized, double-blind, parallel-group, placebo-controlled study
Rasmussen NB, et al. · The Journal of Headache and Pain · randomised, double-blind, placebo-controlled interventional study, 25 healthy volunteers aged 18-45 receiving PACAP38 and VIP infusions
Infused VIP and PACAP38 produced measurable cranial arterial vasodilation, increased facial blood flow and heart rate, and mild headache in healthy subjects. An anti-PACAP monoclonal antibody markedly reduced the PACAP38-driven responses, providing controlled human data on the acute haemodynamic actions of these peptides.
- 06Human clinical2022
The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial
Youssef JG, et al. · Critical Care Medicine · multicentre placebo-controlled randomised trial, 196 patients with COVID-19 respiratory failure, 2:1 allocation, 10 US hospitals
The primary endpoint of being alive and free from respiratory failure at day 60 did not reach statistical significance (OR 1.6, 95% CI 0.86-3.11). A secondary analysis reported improved 60-day survival (OR 2.0, 95% CI 1.1-3.9, p=0.035) alongside reduced interleukin-6 release by day 3.
- 07Human clinical2010
Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis
Prasse A, et al. · American Journal of Respiratory and Critical Care Medicine · open-label phase II study, 20 patients with histologically confirmed active sarcoidosis, 4 weeks of nebulised VIP
Inhaled VIP was well tolerated and significantly reduced TNF-alpha production by cells from bronchoalveolar lavage fluid, while increasing bronchoalveolar CD4+CD127-CD25+ regulatory T cells. This was the first demonstration of an immunoregulatory effect of VIP in humans.
- 08Animal in vivo2026
Heterogeneity between VIP and GRP neurons underlies AVP receptor signaling in the mouse suprachiasmatic nucleus
Zhou H, et al. · Communications Biology · mouse suprachiasmatic nucleus, cell-type-specific expression mapping and conditional V1a deletion with a jet-lag behavioural paradigm
Only a small subpopulation of VIP-ergic ventral suprachiasmatic neurons expressed the vasopressin V1a receptor, and V1a in those VIP neurons was required to maintain circadian robustness in a jet-lag paradigm. V1a expression was minimal in the neighbouring gastrin-releasing peptide population, indicating functional heterogeneity within the ventral SCN.
- 09Animal in vivo2007
Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene
Said SI, et al. · Circulation · VIP gene knockout (VIP-/-) mice versus wild-type controls, haemodynamic and histological assessment
VIP-knockout mice developed moderate right ventricular hypertension, right ventricular hypertrophy and pulmonary vascular remodelling with increased muscularisation and perivascular inflammatory infiltrates, in the absence of systemic hypertension or hypoxaemia. The findings supported VIP deficiency as a contributor to pulmonary arterial hypertension.
- 10Animal in vivo2005
Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons
Aton SJ, et al. · Nature Neuroscience · Vip-/- and Vipr2-/- knockout mice, behavioural recording plus multielectrode recording of suprachiasmatic nucleus neurons
Loss of VIP or the VPAC2 receptor abolished circadian firing rhythms in roughly half of suprachiasmatic nucleus neurons and disrupted synchrony between the remaining rhythmic neurons. Daily application of a VPAC2 agonist restored rhythmicity and synchrony in Vip-/- but not Vipr2-/- slices.
- 11In vitro2026
Finding functional gaps: integrative analysis of VPAC1- and VPAC2-mediated signalling pathways in human lymphocytes
Cabrera-Martín A, et al. · Cell & Bioscience · BRET receptor-G protein coupling assays and stable Jurkat T-cell lines overexpressing VPAC1 or VPAC2
VPAC1 was shown to couple to both Galpha-s and Galpha-q subunits, and the two receptors produced distinguishable second-messenger, kinase-phosphorylation and immune-mediator transcriptional profiles in T cells. The study mapped functional differences between VPAC1 and VPAC2 signalling in a human lymphocyte background.
- 12Review2026
A Historical Review of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide in Sepsis
Dawlaty R, et al. · Biology (Basel) · historical narrative review spanning five decades of VIP and PACAP sepsis research
The review traced VIP and PACAP from early endotoxemia studies, where rising VIP correlated with hypotension and mortality, to their later classification as macrophage-deactivating factors that downregulate TNF-alpha and IL-6. It concluded that the net effect is context-dependent, varying with timing, tissue compartment and inflammatory state.
- 13Review2023
The role of vasoactive intestinal peptide in pulmonary diseases
Zhong HL, et al. · Life Sciences · narrative review of VIP across pulmonary disease states
The review surveyed VIP in pulmonary arterial hypertension, COPD, asthma, cystic fibrosis, acute lung injury/ARDS, pulmonary fibrosis and lung tumours. It identified rapid degradation and short duration of action as the principal limitations of native VIP as a therapeutic and summarised extended-release formulations and analogues under investigation.
- 14Review2012
Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1
Harmar AJ, et al. · British Journal of Pharmacology · IUPHAR consensus receptor pharmacology review
The review established the nomenclature and pharmacology of the three class B receptors PAC1, VPAC1 and VPAC2, noting that PAC1 is PACAP-selective while VPAC1 and VPAC2 bind both VIP and PACAP with high affinity. It catalogued roles spanning circadian rhythm control, immune regulation and smooth muscle relaxation.
- 15Review2008
Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction
Dinsmore WW, Wyllie MG · BJU International · narrative review of the aviptadil/phentolamine (Invicorp) intracavernosal combination
The review summarised the pharmacological rationale and clinical development of the VIP/phentolamine intracavernosal combination as an alternative to alprostadil, emphasising its lower incidence of injection-site pain.
What this evidence does not establish.
The largest and most rigorous randomised trial of intravenous aviptadil in COVID-19 respiratory failure was negative, and meta-analysis of the randomised evidence shows no survival benefit in ARDS, so positive signals from small inhaled-route trials, case series and retrospective cohorts remain unconfirmed. No adequately powered randomised outcome trials exist for VIP or aviptadil in pulmonary arterial hypertension or sarcoidosis; native VIP has a very short plasma half-life, and long-acting analogues such as PB1046 (vasomera) have no primary peer-reviewed trial reports indexed in PubMed as of August 2026.
Common questions about the research.
- What is VIP?
VIP is vasoactive intestinal peptide, a 28-amino-acid neuropeptide isolated from porcine small intestine in 1970 and named for the vasodilator activity that first identified it. It signals through the VPAC1 and VPAC2 receptors and is studied in both vascular and immunological research.
- Why does the literature use an intranasal route as well as injection?
The native peptide has a short circulating half-life, so published work has explored delivery routes that reach target tissue more directly — inhaled delivery in the pulmonary studies, and intranasal administration elsewhere in the neuropeptide literature. Both routes appear as study design choices, not as evidence that one outperforms the other.
- How does VIP relate to PACAP and secretin?
All three belong to the secretin/glucagon peptide superfamily and share receptor overlap. PACAP binds PAC1 with high affinity and also engages VPAC1 and VPAC2; VIP has the reverse preference, favouring VPAC1 and VPAC2 with lower PAC1 affinity. The distinction matters when interpreting studies that use one ligand to infer the behaviour of another.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.