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.
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Compound Profile
Pentapeptide-18 (Leuphasyl)
Key Data
Research reference only
Research Focus
Preclinical data
⚠ 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.
- 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
In Plain English
Simple summaryPentapeptide-18 (Leuphasyl) is a cosmetic peptide designed to complement argireline's SNARE-inhibiting approach to wrinkle reduction. While argireline competes with SNAP-25 at the SNARE complex, Leuphasyl targets a different upstream point -- it acts as an enkephalin analogue, activating delta-opioid receptors on sensory neurons to reduce the neuromuscular signaling that drives facial muscle contraction. In the signaling pathway: enkephalin activates delta-opioid receptors, which reduces adenylate cyclase activity, which reduces cAMP, which ultimately dampens the intensity of neuromuscular junction firing. The brand study pairing Leuphasyl with argireline showed additive wrinkle reduction compared to either alone.
- Opioid receptor-mediated muscle relaxation in skin
- Reduces the depth of expression wrinkles
- Works via different mechanism to Argireline
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is Pentapeptide-18 (Leuphasyl)?
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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
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on Pentapeptide-18 (Leuphasyl). See all Skin & Anti-Aging peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
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.
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
Applied topically to face, particularly around expression lines.
What the research doesn't show
Leuphasyl's delta-opioid receptor mechanism is pharmacologically plausible -- opioid receptor activation does reduce cAMP and can modulate neural signaling. However, the opioid receptor distribution in facial skin/dermis and whether topical pentapeptide concentrations actually produce meaningful receptor activation in humans is not independently established. The 'additive with argireline' study is from the ingredient supplier (Lipotec).
Medical Expert Videos
Physicians, researchers, and pharmacologists explain Pentapeptide-18 (Leuphasyl), covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
Pentapeptide-18 (Leuphasyl) has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: opioid receptor-mediated muscle relaxation in skin.
The most commonly reported side effect in research subjects is well tolerated; no systemic opioid effects from topical use. It is a research chemical, not approved for human use.
Frequently Asked Questions
Explore Further
Quick Reference
How It Compares
Argireline targets SNAP-25 at the SNARE complex; Leuphasyl targets delta-opioid receptors upstream. Syn-Ake targets nicotinic acetylcholine receptors at the neuromuscular junction itself. Snap-8 is an extended argireline analogue. In cosmetic formulation, the combination of Leuphasyl + argireline is the most commonly cited pairing, targeting two different points in the muscle contraction pathway.
Compare Pentapeptide-18 (Leuphasyl) side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.