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Explore  /  Pentapeptide-18 (Leuphasyl)
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Pentapeptide-18 (Leuphasyl)

D
lead outcome
Topical: appearance of expression lines
grades vary by outcome ↓
Peptide
also called — Pentapeptide-18 · Leuphasyl (trade name, Lipotec / Lubrizol) · enkephalin-derived peptide · INCI: Pentapeptide-18
skin appearance (cosmetic)expression lines / dynamic wrinkles
In brief

Pentapeptide-18 (sold as Leuphasyl) is a synthetic five-amino-acid peptide derived from enkephalin, marketed alongside Argireline as an "expression-line" peptide. Where Argireline mimics SNAP-25, Pentapeptide-18 takes a different route — modulating enkephalin receptors that regulate neurotransmitter release at the neuromuscular junction — and the two are sold as synergistic. But it shares the class's core problem: the human evidence is small and largely supplier-linked, much of it from combination products, and it is doubtful that enough peptide crosses intact skin at cosmetic doses to act on muscle. It is a cosmetic ingredient only; it is not botulinum toxin and has never been compared to it.

Legal standing, by region
European Union
Lawful cosmetic ingredient

Lawful cosmetic ingredient (INCI Pentapeptide-18) under EU Regulation 1223/2009; sold over-the-counter. No drug filing. The constraint is claims, not legality of sale.

International
Lawful cosmetic ingredient

Marketed globally as a cosmetic peptide (Leuphasyl).

Evidence, by outcome
How we grade →

An honest grade per outcome — drawn from the evidence, not any catalogue. Hype and undemonstrated marketing claims grade low.

OutcomeEvidence base · effectGrade
Topical: appearance of expression lines
Data are small and supplier-linked; much of the signal is from combination products, not the peptide alone. Independent replication is limited.
Small, largely manufacturer-associated cosmetic evaluations reporting reduced appearance of expression wrinkles, often in combination with acetyl hexapeptide-8 (the two are marketed as synergistic). · Modest reduction in wrinkle appearance reported in some studies.
D
Reaching the neuromuscular junction at cosmetic doses (the premise)
Like other "expression-line" peptides, it must cross the stratum corneum to reach the neuromuscular junction; whether enough does at cosmetic concentrations is unproven.
Penetration data for topical peptides generally · Doubtful
D
"Works like Botox" / muscle relaxation
No trial compares it to botulinum toxin; the mechanism is entirely different (receptor modulation of neurotransmitter release, reversible), and marketing overstates it.
None (no head-to-head) · Not demonstrated
F
Safety (topical)
Regarded as safe as used; independent long-term data limited.
Broad cosmetic use; reported well tolerated · Well tolerated, non-irritating
—
Disclosure

Vallydia sells its own cosmetic serums, and some ingredients graded here belong to the same categories as those products. Grades are drawn from the published evidence by the method we publish, and applied to our own ingredients on the same terms — our copper-peptide serum is graded no more kindly than the peptides it competes with. We disclose the interest so you can weigh it.

Trade names shown here (for example Matrixyl, Argireline, Syn-Ake) are the property of their respective owners and are used only to identify the ingredient under discussion. Their appearance implies no affiliation with, or endorsement by, the proprietor.

Evidence changes

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Cosmetic claims boundary
✓ Allowed (appearance / feel)
  • helps reduce the appearance of expression lines
  • for smoother-looking skin
  • targets the look of fine lines
✕ Not allowed (medicinal)
  • topical botox
  • botox in a jar
  • botox alternative
  • relaxes muscles
  • inhibits muscle contraction
  • reduces neurotransmitter/acetylcholine release
  • freezes wrinkles

The medicinal-sounding science stays in the reference section; product copy speaks only to appearance/feel (Reg 655/2013). Different fields, never merged.

The honest part

Pentapeptide-18 is a cosmetic ingredient framed around the appearance of expression lines, not a muscle treatment. Its enkephalin-receptor mechanism is a different route from Argireline's, but it faces the same two honest limits: small, largely manufacturer-linked evidence (much of it from combination products), and real doubt about whether enough crosses intact skin to act. It is not botulinum toxin and has never been compared to it.

Identity

Pentapeptide-18, marketed as Leuphasyl, is a synthetic five-amino-acid peptide derived from enkephalin, used as a cosmetic active under the INCI name Pentapeptide-18. It belongs to the same "expression-line" family as Argireline and is most often sold with it, on a synergy claim.

Mechanism (as proposed)

Where Argireline mimics the SNAP-25 protein to interfere with SNARE assembly, Pentapeptide-18 works one step upstream: it is proposed to act on enkephalin receptors that regulate the release of acetylcholine at the neuromuscular junction, damping the neurotransmitter signal that triggers muscle contraction. Combining the two — one modulating the receptor, one the SNARE machinery — is the basis of the "synergy" marketing. The mechanism is a genuinely different route, and reversible by nature — nothing like botulinum toxin's enzymatic, irreversible cleavage. The honest gaps are identical to the rest of the class: receptor modulation shown mostly in vitro, and real doubt about whether enough peptide reaches the neuromuscular junction through intact skin at cosmetic concentrations.

Reading the evidence honestly

The clinical record is small and largely supplier-associated, and a large share of it involves combination products rather than the peptide alone — which makes attribution to Pentapeptide-18 specifically difficult. Independent replication is limited. That is why the grade sits at D, and why the "works like Botox" claim is graded F: there is no head-to-head comparison with botulinum toxin, and the mechanism is fundamentally different. As a cosmetic ingredient it is lawful and well tolerated; the constraint is the claims, not the sale.

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Sources — 2 cited
01Manufacturer (Lipotec / Lubrizol) technical dossiers and cosmetic evaluations for Leuphasyl (Pentapeptide-18), including combination studies with acetyl hexapeptide-8.
02Reviews of neurotransmitter-modulating cosmetic peptides and their skin- penetration limits.
Updated 2026-08-07

Grades reflect the published evidence, not our interest. No dosing, reconstitution, or administration is published for research compounds — that restraint is deliberate.

Related compounds
Argireline (Acetyl Hexapeptide-8)C
Peptide
SNAP-8 (Acetyl Octapeptide-3)C
Peptide
Matrixyl (Palmitoyl Pentapeptide-4)B
Peptide
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This site provides neutral scientific reference and sells only products lawful in your region. Nothing here is medical advice, a recommendation, or an offer to supply unapproved medicines. No dosing or administration is published for research compounds. Cosmetic peptides per Regulation (EC) 1223/2009. Unapproved injectable peptides are neither sold nor advertised in the EU (Directive 2001/83/EC, Title VIII). © 2026 Vallydia.