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

PACAP-38 vs VIP (Vasoactive Intestinal Peptide) — Peptide Comparison PACAP-38 vs VIP (Vasoactive Intestinal Peptide) — compare dosing, benefits, safety profiles, side effects, and how they stack. See which peptide is right for… At a Glance Dose Range PACAP-38 5 pmol/kg/min–20 pmol/kg/min mg VIP (Vasoactive Intestinal Peptide) 67 mcg/day–300 mcg/day mcg Frequency Once daily Administration Intravenous infusion Cycle Length Ongoing/indefinite Onset Speed Moderate (1-2 weeks) Evidence Level Strong human trials (Phase 3 or FDA approved) Moderate human trials (Phase 1-2) Efficacy Neuroprotection Anti-Inflammatory Migraine Research Cardiovascular Technical Data Molecular Formula C203H331N63O53S Molecular Weight ~4534 Da Half-Life Very short plasma half-life (minutes); rapid enzymatic degradation Bioavailability IV: systemic; Intranasal: direct CNS access bypassing BBB; poor oral bioavailability CAS Number 137061-48-4 C147H237N43O43S 3325.83 Da Approximately 1-2 minutes in plasma (rapid enzymatic degradation) IV: 100%; Inhaled: local pulmonary delivery; short systemic half-life 37221-79-7 Protocols standard 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. 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). 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. Applications 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. 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. Safety Profile Common Flushing Tachycardia Gastrointestinal Effects Transient Warmth Sensation Uncommon Headache and Migraine Triggering Hypotension Serious Systemic Hypotension and Cardiovascular Effects Systemic Inflammatory Activation Facial Flushing Diarrhea Nausea Cardiovascular Effects Severe Flushing and Facial Erythema Research Status FDA Status Research compound Safety Overview 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. Contraindications 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 xInsufficient data for pregnancy and lactation safety 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. xUncontrolled hypotension or hemodynamic instability xSevere cardiac decompensation xNot approved for clinical use outside of trials Decision Guide Choose PACAP-38 if... Neuroprotection research Stroke and traumatic brain injury investigation Migraine pathophysiology studies Anti-inflammatory mechanism research Choose VIP (Vasoactive Intestinal Peptide) if... Pulmonary arterial hypertension research ARDS and respiratory failure investigation Anti-inflammatory therapy development Neuroprotection studies