New — Free Peptide Starter Guide (2026): 13 chapters, 34 cited studies

Get it free
ToolsComparePE-22-28 vs Pentapeptide-18

PE-22-28 vs Pentapeptide-18

Side-by-side comparison of key properties, dosing, and research.

Cognitive Enhancement
PE-22-28
Skin & CosmeticAnti-Aging & Longevity
Pentapeptide-18
Summary
PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
Pentapeptide-18 (Leuphasyl) is a synthetic pentapeptide that mimics the sequence of enkephalin, an endogenous neuropeptide. It acts on neuronal pain receptors in facial muscles to reduce muscle contraction intensity and depth of expression lines, functioning similarly to Argireline (Acetyl Hexapeptide-3) but via a different receptor mechanism.
Half-Life
Relatively short; CNS effects may persist due to neurogenic mechanisms
Not applicable (topical)
Admin Route
SubQ, Intranasal
Topical
Research
Typical Dose
200–400 mcg
0.005–0.05% in formulation
Frequency
Once daily
Twice daily
Key Benefits
  • Rapid-onset antidepressant effects (within 24 hours)
  • Promotes hippocampal neurogenesis
  • Improves cognitive performance and memory
  • Reduces anxiety and depressive behavior
  • Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
  • May help treatment-resistant depression
  • Neuroprotective effects
  • Reduces depth of expression lines (forehead, crow's feet, glabellar)
  • Inhibits acetylcholine release for muscle-relaxing effect
  • Complementary mechanism to Argireline for enhanced anti-wrinkle activity
  • Reversible and well-tolerated
  • No risk of systemic paralysis at cosmetic concentrations
  • Suitable for daily use in serums and creams
Side Effects
  • Generally well tolerated in animal models
  • Limited human data available
  • Possible mild headache or transient mood changes at initiation
  • Injection site reactions (SC)
  • Generally very well-tolerated topically
  • Rare skin sensitivity or mild irritation
  • Theoretical opioid receptor desensitization with very prolonged high-dose use (not documented cosmetically)
Stacks With