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ToolsComparePentapeptide-18 vs PE-22-28

Pentapeptide-18 vs PE-22-28

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

Skin & CosmeticAnti-Aging & Longevity
Pentapeptide-18
Cognitive Enhancement
PE-22-28
Summary
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.
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.
Half-Life
Not applicable (topical)
Relatively short; CNS effects may persist due to neurogenic mechanisms
Admin Route
Topical
SubQ, Intranasal
Research
Typical Dose
0.005–0.05% in formulation
200–400 mcg
Frequency
Twice daily
Once daily
Key Benefits
  • 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
  • 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
Side Effects
  • Generally very well-tolerated topically
  • Rare skin sensitivity or mild irritation
  • Theoretical opioid receptor desensitization with very prolonged high-dose use (not documented cosmetically)
  • Generally well tolerated in animal models
  • Limited human data available
  • Possible mild headache or transient mood changes at initiation
  • Injection site reactions (SC)
Stacks With