Skin & Anti-Aging

Pentapeptide-18 (Leuphasyl)

Pentapeptide-18 (Leuphasyl) is a synthetic enkephalin-mimetic pentapeptide that acts on opioid receptors in skin to relax facial muscles and reduce expression lines.

C30H50N6O9Half-life: Topical; local actionMolar mass: 642.75 g/mol

⚠ Research & Educational Use Only. Pentapeptide-18 (Leuphasyl) is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.

Medically reviewed by Dr. Amanda Reid, MDWritten by the KnowYourPeptide Research TeamLast updated April 2026
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Key Takeaways
  • Opioid receptor-mediated muscle relaxation in skin
  • Reduces the depth of expression wrinkles
  • Works via different mechanism to Argireline
  • Pentapeptide-18 (Leuphasyl) is not FDA-approved for human use. Cosmetic ingredient. No systemic regulatory approval needed for topical use.

Research At a Glance

  • Opioid receptor-mediated muscle relaxation in skin
  • Reduces the depth of expression wrinkles
  • Works via different mechanism to Argireline
  • Synergistic with Acetyl Hexapeptide-3

What is Pentapeptide-18 (Leuphasyl)?

Pentapeptide-18 (commercial name: Leuphasyl) is a synthetic pentapeptide with the sequence Tyr-D-Ala-Gly-Phe-Leu. Its design is based on the endogenous opioid peptide Leu-enkephalin, which naturally modulates pain transmission and muscle contraction via delta opioid receptors. Pentapeptide-18 targets opioid receptors expressed in skin and cutaneous sensory nerve endings to modulate the signaling cascade that leads to facial muscle contraction.

What It Is

  • A synthetic enkephalin-mimetic pentapeptide (Leu-enkephalin analogue)
  • Acts via delta opioid receptors in skin and cutaneous nerves
  • Designed to complement neurotransmitter-blocking peptides like Argireline (Acetyl Hexapeptide-3)
  • INCI name: Pentapeptide-18; commercial name: Leuphasyl

How It Works

  • Binds delta opioid receptors expressed on cutaneous sensory neurons
  • Activates inhibitory G-proteins (Gi), reducing cyclic AMP and suppressing neurotransmitter release at the neuromuscular junction
  • Reduces acetylcholine-mediated muscle contraction signals at the skin surface
  • Example: In neuromuscular junction cell culture models, Pentapeptide-18 at 500 mcg/mL reduced vesicle release (acetylcholine proxy) by approximately 20% vs vehicle
  • Acts via a complementary mechanism to Acetyl Hexapeptide-3 (which blocks SNARE complex formation), allowing synergistic effects when combined

Key Research Findings

  • Combination study: In a randomized controlled study, a formulation containing both Pentapeptide-18 (4%) and Argireline (4%) reduced forehead wrinkle depth by 24% at 4 weeks vs 17% for Argireline alone and 15% for Pentapeptide-18 alone
  • Mechanism confirmation: Radioligand binding assays confirmed Pentapeptide-18 competes with Leu-enkephalin for delta opioid receptor binding in skin homogenates
  • Safety: No measurable systemic opioid activity in pharmacokinetic studies; the peptide does not cross the skin barrier in quantities sufficient for central opioid effects

Dosing From the Literature

  • Topical: 2-4% in cream or serum
  • Applied to expression line-prone areas (forehead, crow's feet, glabella)

Storage and Handling

  • Lyophilised: 2-8 degrees C; stable 24 months
  • In formulation: stable at pH 4-7; sensitive to proteolytic degradation above pH 7.5

Key Research Benefits

Documented effects observed in preclinical and clinical studies on Pentapeptide-18 (Leuphasyl). See all Skin & Anti-Aging peptides for comparison.

Opioid receptor-mediated muscle relaxation in skin
Reduces the depth of expression wrinkles
Works via different mechanism to Argireline
Synergistic with Acetyl Hexapeptide-3

Side Effects & Risks

Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports.

Well tolerated; no systemic opioid effects from topical use
Non-irritating in clinical studies

Dosing Data from the Literature

Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.

Research Dosing Protocol

Topical: 2-4% in cream or serum formulations.

Enter your vial size and target dose to get the exact injection volume.

Administration in Research Settings

Standard reconstitution and administration methodology for laboratory research use.

Applied topically to face, particularly around expression lines.

Explore Further

Quick Reference

Half-Life
Topical; local action
Molar Mass
642.75 g/mol
Formula
C30H50N6O9
Legal Status
Cosmetic ingredient. No systemic regulatory approval needed for topical use.
Storage
Store at 2-8 degrees C. Stable at pH 4-7.

Research Use Only

This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.

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