Vasoactive Intestinal Peptide (VIP)
/ Vasoactive Intestinal Peptide; 28-residue secretin-family peptide; VPAC1/VPAC2 receptor agonistALIAS · VIP · Vasoactive intestinal polypeptide
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Tier 3. Endogenous neuropeptide isolated by Said and Mutt in 1970. Several VIP analogs and VIP-receptor agonists have been investigated for pulmonary hypertension, cystic fibrosis, sarcoidosis, and Sjogren syndrome; none are FDA-approved. Aviptadil (synthetic VIP) received emergency-use authorisation discussions during COVID-19 acute respiratory distress trials but was not approved.
VIP is a 28-residue peptide of the secretin/glucagon superfamily, expressed widely in central and peripheral neurons and in enteric, respiratory, and immune tissues. It signals through two class B G-protein-coupled receptors, VPAC1 and VPAC2, both coupled primarily to Gs and adenylyl cyclase, with VPAC2 additionally engaging Gq pathways in some tissues. Pituitary adenylate cyclase activating peptide (PACAP) shares the same receptors and overlapping biology.
Physiologically, VIP is a potent smooth-muscle relaxant and vasodilator (the namesake action), a regulator of bronchial and pulmonary vascular tone, an enteric secretomotor neurotransmitter, a circadian regulator in the suprachiasmatic nucleus, and an anti-inflammatory immunomodulator that biases T-cell responses toward Th2/regulatory phenotypes.
Therapeutic interest has focused on the pulmonary vasodilator and anti-inflammatory actions. Inhaled and intravenous synthetic VIP (aviptadil) has been investigated in pulmonary arterial hypertension, sarcoidosis, and acute respiratory distress syndrome.
No FDA approvals for VIP or VIP analogs. Aviptadil (synthetic VIP) reached Phase 2/3 trials in COVID-19 acute respiratory distress syndrome with mixed results that did not support emergency approval. Small inhaled-VIP studies in pulmonary hypertension and sarcoidosis have shown short-term hemodynamic effects without progression to pivotal trials.
Acute infusion of VIP produces flushing, hypotension, and tachycardia. No long-term safety database. The COVID-19 ARDS aviptadil trials reported no major safety signals at the doses studied but were inconclusive on benefit.
Regulatory status
- FDA status:
- Not FDA-approved
VIP has been described as a 'molecule in search of an indication' - the mechanistic rationale is broad and the preclinical literature is extensive, yet no clinical program has produced an approved product over more than five decades since its isolation.
Vendor-sold VIP material is intended for research use. There is no published clinical or pharmacokinetic data supporting any specific dosing schedule for self-administration, and the peptide's short half-life and strong systemic vasodilator effects make peripheral administration unforgiving.