Pentapeptide-18
Also known as: Leuphasyl, YAGFL, enkephalin analog pentapeptide
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
Not applicable (topical)
Route
Topical
Category
Skin & Cosmetic, Anti-Aging & Longevity
Studies
4 references
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
Mechanism of Action
Pentapeptide-18 binds to delta-opioid receptors on nerve terminals, mimicking enkephalin signaling to reduce the release of acetylcholine at the neuromuscular junction. This reduces the amplitude of muscle contractions in facial expression muscles, decreasing the formation of dynamic wrinkles. Unlike botulinum toxin, the effect is reversible and dose-dependent without complete paralysis. When combined with Argireline (which acts on SNAP-25), the two peptides provide complementary inhibition of neurotransmitter release.
Dosing Protocols
Expression Line Reduction (Standard)
- Dose
- 0.005–0.05% in formulation
- Frequency
- Twice daily
- Timing
- AM and PM after cleansing, target expression-prone areas
- Cycle
- 8–12 weeks, ongoing
Best combined with Argireline (0.5–1%) for synergistic dual-mechanism anti-wrinkle effect. Apply to forehead, periorbital area, and nasolabial folds. Some formulations combine all three: Pentapeptide-18, Argireline, and SNAP-8.
Calculate your draw volume
Enter your vial size and BAC water to get exact injection volumes
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)
Contraindications
Known opioid peptide sensitivityCaution in pregnancy (insufficient data)
Storage
Store at room temperature in a sealed container away from light. Stable in slightly acidic to neutral pH formulations. Avoid excessive heat.
Clinical Research
- 1.Pentapeptide-18 as an anti-aging candidate: Spectroscopic characterization and molecular interaction analysis
Akhan D, Bicak B, Akalin E, Gunduz SK · Computational biology and chemistry · 2026PubMed Verified
- 2.Retinol and Oligopeptide-Loaded Lipid Nanocarriers as Effective Raw Material in Anti-Acne and Anti-Aging Therapies
Pawłowska M, Marzec M, Jankowiak W, Nowak I · Life (Basel, Switzerland) · 2024PubMed Verified
- 3.Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application
Pawłowska M, Marzec M, Jankowiak W, Nowak I · International journal of molecular sciences · 2024PubMed Verified
- 4.D-tyrosine adds an anti-melanogenic effect to cosmetic peptides
Park J, Jung H, Jang B, Song HK, Han IO, Oh ES · Scientific reports · 2020PubMed Verified
Medical disclaimer: This information is for educational purposes only and does not constitute medical advice. Many compounds listed are research chemicals not approved for human use. Always consult a qualified healthcare professional before starting any protocol.
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