VIP (Vasoactive Intestinal Peptide) vs PACAP-38 — Peptide Comparison

At a Glance

Quickcomparison

Dose Range

VIP (Vasoactive Intestinal Peptide)

67 mcg/day–300 mcg/day mcg

PACAP-38

5 pmol/kg/min–20 pmol/kg/min mg

Frequency

Once daily

Administration

Intravenous infusion

Cycle Length

Ongoing/indefinite

Onset Speed

Moderate (1-2 weeks)

Evidence Level

Moderate human trials (Phase 1-2)

Strong human trials (Phase 3 or FDA approved)

Efficacy

Benefitratings

Cardiovascular

Anti-Inflammatory

Neuroprotection

Migraine Research

Technical Data

Compoundspecifications

Molecular Formula

C147H237N43O43S

Molecular Weight

3325.83 Da

Half-Life

Approximately 1-2 minutes in plasma (rapid enzymatic degradation)

Bioavailability

IV: 100%; Inhaled: local pulmonary delivery; short systemic half-life

CAS Number

37221-79-7

C203H331N63O53S

~4534 Da

Very short plasma half-life (minutes); rapid enzymatic degradation

IV: systemic; Intranasal: direct CNS access bypassing BBB; poor oral bioavailability

137061-48-4

Protocols

Dosingtiers

starting

50 mcg

Twice daily (morning and evening)

Ongoing per protocol

Common research/community practice dose for systemic/peripheral effects (approx., not from a controlled trial).

standard

50 mcg per inhalation (200 mcg/day); 100 mcg single acute dose

Four inhalations daily

12 weeks (chronic study)

Inhaled aviptadil in primary pulmonary hypertension: 4 inhalations/day; single 100 mcg dose used for acute vasoreactivity testing [7].

advanced

50 → 100 → 150 pmol/kg/hr (ascending over 3 days)

12-hour infusion daily

3 consecutive days

Aviptadil (ZYESAMI) dose-escalation regimen in critical COVID-19 respiratory failure trials [6]. Hospital/investigational only.

10 pmol/kg/min

Continuous infusion

20-minute single infusion

Standardized human experimental-medicine provocation dose; 10 pmol/kg/min over 20 min was selected as the optimal/maximum tolerated rate after dose-finding (5-20 pmol/kg/min) and is reproduced across headache-model trials [6][7][8]. Used as a research provocation agent, not an approved therapeutic.

Applications

Bestsuited for

Pulmonary arterial hypertension research

VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on pulmonary arterial hypertension research. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

ARDS and respiratory failure investigation

VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on ards and respiratory failure investigation. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Anti-inflammatory therapy development

VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on anti-inflammatory therapy development. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Neuroprotection studies

VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on neuroprotection studies. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Neuroprotection research

PACAP-38 is particularly well-suited for individuals focused on neuroprotection research. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Stroke and traumatic brain injury investigation

PACAP-38 is particularly well-suited for individuals focused on stroke and traumatic brain injury investigation. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Migraine pathophysiology studies

PACAP-38 is particularly well-suited for individuals focused on migraine pathophysiology studies. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Anti-inflammatory mechanism research

PACAP-38 is particularly well-suited for individuals focused on anti-inflammatory mechanism research. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Safety Profile

Sideeffects

Common

Facial Flushing

Diarrhea

Nausea

Uncommon

Hypotension

Tachycardia

Cardiovascular Effects

Serious

Severe Flushing and Facial Erythema

Flushing

Gastrointestinal Effects

Transient Warmth Sensation

Headache and Migraine Triggering

Systemic Hypotension and Cardiovascular Effects

Systemic Inflammatory Activation

Research Status

Safety& evidence

FDA Status

Research compound

Safety Overview

VIP (Vasoactive Intestinal Peptide) is a 28-amino acid endogenous neuropeptide with moderate evidence from Phase 1-2 human clinical trials. The synthetic pharmaceutical form (aviptadil/RLF-100) received FDA fast-track designation for COVID-19-associated ARDS, indicating recognition of its therapeutic potential. Critical safety considerations: VIP is a potent vasodilator that causes dose-dependent hypotension and compensatory tachycardia—hemodynamic monitoring is essential during IV administration. Common side effects include facial flushing and diarrhea from its GI effects. Phase 2b/3 COVID-19 ARDS trials (196 patients) reported NO serious drug-related adverse events, a favorable safety signal. However, individual responses to vasodilation vary significantly based on baseline cardiovascular status, medications, and underlying conditions. The peptide's short plasma half-life (1-2 minutes) limits systemic accumulation. Inhaled VIP shows excellent local tolerability for pulmonary applications with minimal systemic absorption.

Contraindications

xUncontrolled hypotension or hemodynamic instability

xSevere cardiac decompensation

xNot approved for clinical use outside of trials

xInsufficient data for pregnancy and lactation safety

PACAP-38 shows good tolerability in Phase II trials for migraine and pain conditions with minimal serious adverse events at IV doses of 2-6 mcg/kg. Primary side effects are transient flushing and headache (10-15% of subjects), likely related to vasodilation. Cardiovascular effects include mild heart rate increase and blood pressure changes, monitored in clinical settings. No carcinogenicity or teratogenicity in animal models; limited long-term safety data in humans.

xActive migraine or headache disorder (PACAP-38 is a potent migraine trigger)

xUncontrolled hypotension or cardiovascular instability

xNot approved for clinical use outside research settings

Decision Guide

Which isright for you?

Choose VIP (Vasoactive Intestinal Peptide) if...

Pulmonary arterial hypertension research

ARDS and respiratory failure investigation

Anti-inflammatory therapy development

Neuroprotection studies

Choose PACAP-38 if...

Neuroprotection research

Stroke and traumatic brain injury investigation

Migraine pathophysiology studies

Anti-inflammatory mechanism research