Leuphasyl

pentapeptide-18, Tyr-D-Ala-Gly-Phe-Leu, Leuphasyl (Lipotec trade name), "enkephalin-mimic peptide"

Skin & cosmetic

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic five-amino-acid peptide; an analogue of leucine-enkephalin (the body's natural opioid pentapeptide) with a D-alanine substitution to resist breakdown
Mechanism: Proposed to activate enkephalin (opioid) receptors on nerve endings, which lowers calcium entry and so reduces the amount of acetylcholine released at the neuromuscular junction
Routes studied: Topical only
Dose range reported: Company study: 5% of the raw solution twice daily for 28 days, alone and combined with Argireline. Finished products typically contain 2–5%
Half-life: Not applicable systemically; local action intended
Storage: Finished products as labelled; raw solution refrigerated
Regulatory status: Permitted cosmetic ingredient worldwide

Doses are as reported in studies or by the community — never recommendations.

1What it is

Leuphasyl is a synthetic peptide from Lipotec (now Lubrizol), launched around 2005 as a partner for Argireline (#50). Its sequence copies leucine-enkephalin — a natural pentapeptide the nervous system uses to dampen pain and nerve signalling — but with one amino acid swapped to the D-form, the same trick used in enkephalin analogues studied as painkillers decades ago, so that skin enzymes do not destroy it instantly.

It is a synthetic analogue of a natural molecule, not the natural molecule itself. It is the least discussed of the "neuro-cosmetic" trio (Argireline, Snap-8, Leuphasyl) and is rarely sold alone; it mostly appears in combination formulas aimed at expression lines.

2How it's thought to work

Enkephalins bind opioid receptors (mainly δ and μ) on nerve terminals. Activation closes calcium channels and opens potassium channels, making the terminal less excitable and reducing the release of neurotransmitter.

Leuphasyl is proposed to do this at the motor nerve endings beneath facial skin, releasing less acetylcholine per impulse.

Because Argireline acts further down the same pathway (on SNARE assembly), the manufacturer proposes an additive effect when the two are combined.

Proposed: a pentapeptide said to act on the nerve ending through enkephalin receptors rather than the SNARE complex, reducing the transmitter released.Schematic — not to scale

As with the others in this class, the limiting question is whether a water-soluble pentapeptide crosses intact skin to reach nerve endings. There are no independent data. Enkephalin receptors also exist on keratinocytes and skin nerve fibres, so some reported "soothing" effects could be epidermal.

3What the research shows

Expression wrinkles

The manufacturer's 28-day test in around 20 volunteers reported an average reduction in crow's-feet wrinkle depth of roughly 11% with 5% Leuphasyl alone and roughly 25% when 5% Leuphasyl was combined with 5% Argireline, versus placebo (Lipotec technical dossier; summarised in Reddy 2012 and Schagen 2017). Small, open-label on the single-agent arm, and industry-run. [1][2]

Reduced neurotransmitter release in cells

Company cell-culture work on glutamate release from neurons as a proxy for acetylcholine release.

Independent trials

None published. No peer-reviewed study isolates Leuphasyl's contribution in any finished product.

4Reported side effects and interactions

Literature-reported

No adverse events in company testing; standard irritation and sensitisation panels passed.

Community-reported

mild stinging rarely; most reports are of subtle or no effect, and users seldom distinguish its effect from the Argireline it is paired with.

Theoretical. systemic opioid effects would require absorption far beyond what topical cosmetic use could plausibly deliver; none reported. People sensitive to opioids have no documented reason for concern but no data either.

Interactions. none pharmacological. Combined routinely with Argireline (#50) and Snap-8 (#113).

Markers researchers commonly monitor

No lab markers apply to a topical cosmetic. No compound-specific monitoring is established. The literature is thin, and this profile is shorter for that reason.

Marker	Why it's watched
Photographs at rest and at full expression, identical lighting, every 2–4 weeks
Irritation diary

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Topical only. Supplied as a finished cosmetic or a raw aqueous solution for formulators. Store as labelled; refrigerate raw solution. No injectable form exists and none should be improvised — injecting an opioid-receptor peptide of unknown purity has no research rationale. The calculator does not apply.

Open in calculator, pre-loaded →

6Commonly studied alongside

Argireline (#50) — almost always paired; Snap-8 (#113); Syn-Ake (#114); Matrixyl 3000 (#112) for matrix support in the same formula.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Permitted cosmetic ingredient; nerve-signal or muscle-relaxing claims would be drug claims under FDA rules
European Union	Permitted under EC 1223/2009; listed in CosIng
United Kingdom	Same as EU
Australia	Cosmetic ingredient
South Africa	Cosmetic ingredient
Sport	Not listed by WADA

8Open questions

Any skin-penetration data at all, independent of the manufacturer.
Whether the additive effect with Argireline holds in a blinded, independent trial.
Whether the natural opioid receptor system in skin contributes to any observed effect, separate from the neuromuscular story.

9References

1Reddy BY, Jow T, Hantash BM (2012). Bioactive oligopeptides in dermatology: Part II. Exp Dermatol. PubMed · DOI
2Schagen SK (2017). Topical peptide treatments with effective anti-aging results. Cosmetics. DOI
3Lupo MP, Cole AL (2007). Cosmeceutical peptides. Dermatol Ther. PubMed · DOI
4Blanes-Mira C et al. (2002). A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci (the partner compound). PubMed · DOI
5Lipotec / Lubrizol (manufacturer technical dossier). Leuphasyl efficacy summary — company data, not peer-reviewed. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

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community protocols include this →

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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