Vasoactive Intestinal Peptide

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide that acts as a vasodilator, smooth muscle relaxant, and anti-inflammatory agent via VPAC1/VPAC2 G-protein-coupled receptors, with investigational uses in managing chronic inflammatory response syndrome, pulmonary hypertension, and glucose-dependent insulin secretion.

Brief glance

The primary outcome is Immune Support, but it's also used for Metabolic, Recovery & Repair. This compound is considered a Peptide. It is not currently indicated as compoundable in 503A pharmacies. It is not listed under a DEA schedule.

Overview

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide that acts as an active pharmaceutical ingredient via G protein-coupled receptors (VPAC1, VPAC2, PAC1), exhibiting anti-inflammatory, immunomodulatory, and bronchodilatory effects. It suppresses pro-inflammatory cytokines and promotes anti-inflammatory mediators, showing therapeutic potential in autoimmune diseases like rheumatoid arthritis and multiple sclerosis, as well as respiratory disorders such as asthma and pulmonary hypertension. VIP has been investigated in clinical trials for conditions including sepsis, inflammatory bowel disease, and neurodegenerative disorders, with administration often via intranasal spray.

Vasoactive intestinal peptide (VIP), a 28-amino acid peptide hormone belonging to the glucagon/secretin superfamily, acts primarily as a ligand for class II G protein-coupled receptors VPAC1 and VPAC2. It functions as a potent vasodilator, smooth muscle relaxant, and secretagogue, stimulating water and electrolyte secretion in the intestine, pancreatic bicarbonate release, and inhibiting gastric acid secretion while promoting gut motility. Pharmacologically, VIP exhibits anti-inflammatory and immunomodulatory effects by suppressing pro-inflammatory cytokines like TNF and IL-12 while enhancing anti-inflammatory IL-10 in immune cells. Research highlights its potential therapeutic role in inflammatory conditions such as rheumatoid arthritis and Crohn's disease through inhibition of T-cell responses and adhesion molecule expression, though it remains investigational as an active pharmaceutical ingredient.

Benefits

Vasoactive Intestinal Peptide (VIP) exhibits immunomodulatory and anti-inflammatory effects, suppressing pro-inflammatory cytokines such as TNF and IL-1 while upregulating anti-inflammatory cytokines like IL-10, which has shown therapeutic potential in experimental models of rheumatoid arthritis by delaying onset, reducing severity, and inhibiting T-cell expansion and autoimmune responses.¹,² In respiratory conditions, VIP relaxes airway smooth muscle, improves airflow, and reduces bronchial constriction, as demonstrated in animal models of respiratory illness.³ Emerging evidence also indicates glucose-dependent insulin secretion via VPAC2 receptors, suggesting potential as an insulinotropic agent without hypoglycemia risk.⁴ These properties position VIP as a candidate for managing autoimmune diseases, chronic inflammation, and septic shock in preclinical studies.²,³

Side effects

Vasoactive Intestinal Peptide (VIP) is a neuropeptide with immunomodulatory and anti-inflammatory properties that has been investigated in clinical research settings.⁵ The most commonly reported adverse effects of VIP administration are cardiovascular and vasodilatory in nature, including flushing, warm sensations, heart palpitations, dizziness, and blood pressure changes, with flushing occurring in approximately 95% of patients receiving intravenous infusion.⁵,⁶ Gastrointestinal side effects such as nausea, diarrhea, and abdominal discomfort have been documented, particularly in susceptible populations including those with migraine disorders.⁵,⁶ Systemic administration of VIP causes a marked decrease in blood pressure and tachycardia, necessitating careful monitoring in patients with uncontrolled hypertension or cardiovascular instability.⁵,⁷ Key safety considerations include avoiding use in patients with active uncontrolled hypertension, exercising caution in those with mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS), or baseline low blood pressure, and discussing potential interactions with vasodilators before administration.⁷,⁸,⁹ The side effect profile appears dose-dependent and route-specific, with nasal spray formulations generally producing localized effects with minimal systemic concerns compared to intravenous or injectable routes.⁸,¹⁰ Clinical use requires provider supervision and dose titration strategies to minimize adverse effects during the adjustment period.

Mechanisms of action

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide that acts as an active pharmaceutical ingredient by binding to VPAC1 and VPAC2 G protein-coupled receptors on cell membranes, triggering activation of adenylate cyclase and a subsequent increase in intracellular cyclic AMP (cAMP) levels.¹¹,¹²,¹³ This cAMP-dependent pathway mediates its primary pharmacological effects, including splanchnic vasodilation via nitric oxide release from endothelial cells and direct action on vascular smooth muscle, inhibition of gastric acid secretion through interactions with somatostatin, and regulation of gastrointestinal motility and ion secretion.¹¹,¹³ In therapeutic contexts, VIP has been investigated for pulmonary arterial hypertension due to its ability to reduce pulmonary vascular resistance and inhibit platelet activation and smooth muscle proliferation, as well as for enhancing glucose-dependent insulin secretion via VPAC2 receptors on pancreatic beta cells.⁴,¹¹ Its receptor-mediated endocytosis and lysosomal degradation contribute to signal termination after binding.¹¹