Pentapeptide-18 is sold to skin care under the trade name Leuphasyl and a promise about expression lines. Under its chemical name it had a long earlier life in a different field entirely, and knowing both halves is the quickest way to see how thin its skin-care file is.
The molecule, under three names
PubChem CID 10099522 resolves pentapeptide-18 to Tyr-D-Ala-Gly-Phe-Leu: formula C29H39N5O7, 569.6 g/mol. The same record lists Leuphasyl and [D-Ala2]leucine-enkephalin as synonyms.
The third name says what the molecule is. Leucine-enkephalin is one of the body's own opioid peptides, five amino acids long. Pentapeptide-18 is that peptide with its second amino acid, glycine, replaced by D-alanine, the mirror-image form of alanine. That substitution is a common one in enkephalin research, where much of this molecule's older literature concerns the enzymes that break enkephalins down.
At 569.6 g/mol it sits a little above the 500-dalton figure usually quoted as the ceiling for passive penetration — lighter than acetyl hexapeptide-8 at 887.
Its first career: an opioid research tool
Searched by its chemical names on 2026-09-21, the molecule appears in 27 PubMed records dated 1979 to 2008: receptor binding, enkephalin-degrading enzymes, NMR studies of its shape in solution. None is about skin. Ten of them date from the 1980s and thirteen from the 1990s.
One trap is worth naming because it inflates any count. Dalargin, a six-residue analogue whose records here sit mostly in Russian journals, begins with the same five amino acids and adds an arginine, so papers about it are written in the same vocabulary: searching the sequence string Tyr-D-Ala-Gly-Phe-Leu returns 23 records, several of them about dalargin, and at least one dalargin paper appears in the 27 above. A sequence or name search matches text; it does not identify a molecule.
None of this history says the cosmetic ingredient acts as an opioid in skin. What it does say is that the molecule is not an obscure cosmetic invention: it is a well-characterised pharmacological analogue that was renamed for a new market. The skin literature mentions the enkephalin resemblance only as a mechanism claim, and does not test it.
Six skin-care records, and what they tested
Searched on 2026-09-21 as pentapeptide-18 or Leuphasyl, with a control query validated in the same session:
| Year | Group | What it is |
|---|---|---|
| 2026 | Istanbul (Akhan et al.) | anticancer activity of venom-derived and neurotransmitter-inhibitor pentapeptides, in vitro and in silico |
| 2026 | Istanbul (Akhan et al.) | docking and simulation of Vialox and Leuphasyl against collagen-degrading enzymes, plus a skin-cell toxicity test |
| 2026 | Istanbul (Akhan et al.) | spectroscopy and docking of pentapeptide-18 |
| 2024 | Poznań (Pawłowska et al.) | retinol + pentapeptide-18 lipid nanoparticles: stability and formulation |
| 2024 | Poznań (Pawłowska et al.) | the same nanoparticles in creams, with volunteers |
| 2020 | Seoul (Park et al.) | adding a D-tyrosine to the peptide to give it an anti-pigment effect, in cells and a 3D skin model |
Three are computer models. Akhan and colleagues' 2026 study in Chemistry & Biodiversity docks Leuphasyl and a second peptide, Vialox, against matrix metalloproteinases and sirtuin-1 and finds no toxicity to skin cells up to 1 mg/mL. Their paper in Computational Biology and Chemistry characterises the molecule by spectroscopy and density-functional theory. Both describe the peptide as a promising anti-ageing agent. Neither tested it on skin in a person.
One changes the molecule. Park and colleagues, Scientific Reports 2020, added a D-tyrosine to the end of pentapeptide-18 and gave it an anti-pigment effect in melanocytes and a 3D skin model. That is a result about a new molecule, not about the ingredient on a label.
The one study with people in it
Pawłowska and colleagues, Life 2024, is the only record in which people applied pentapeptide-18. The anti-ageing panel was 20 women, each given two night creams to use over eight weeks: one containing lipid nanoparticles loaded with retinol and pentapeptide-18 together, and the base cream without the nanoparticles. A second panel of 20 tested an anti-acne version. The authors report fewer facial wrinkles and less irritation than retinol usually causes.
The design cannot say what the peptide did. The two actives arrived in the same particles and left together; there was no arm with retinol alone or peptide alone. Retinol has a far larger file for this job: in the same PubMed session, 29 randomized trials mentioning retinol in the title or abstract concerned wrinkles or photoageing, against none for pentapeptide-18. A wrinkle result from a cream containing both cannot be credited to the one with no file of its own. Two of the four authors were employed by Dottore Polska, the company that made the base creams, as the paper's own conflict statement records.
The claimed mechanism
The Polish authors describe the peptide as acting like the natural enkephalin pathway to reduce acetylcholine release where nerves meet facial muscles — relaxing the muscle contractions that fold skin into expression lines. That places it beside acetyl hexapeptide-8 (Argireline), which aims at the same junction from inside the nerve ending, and SYN-AKE, which aims at the muscle's receptor.
Formulators often put the first two side by side. In The Ordinary's Multi-Peptide + HA Serum pentapeptide-18 is declared fifth, directly after acetyl hexapeptide-8, and its copper-peptide serum keeps the same order. The indexed literature contains no trial of the pair either.
One small irony is worth recording. A 2026 peptide safety framework from Procter & Gamble used enkephalin as one of its examples of a peptide whose biological action its screening tools correctly detect. It did not test pentapeptide-18.
What this supports saying
- Pentapeptide-18, Leuphasyl and [D-Ala2]-leucine-enkephalin are the same molecule, 569.6 g/mol.
- It is an analogue of one of the body's own opioid peptides, with a research record from 1979 to 2008 in opioid and enzyme studies and none in skin.
- Its six skin-care papers are three computer-modelling studies, two formulation papers from one company-linked group, and one study of a modified molecule.
- The only human use paired it with retinol in the same particles, so no effect can be attributed to the peptide.
Where to go next
- Argireline (acetyl hexapeptide-8) — its usual partner on a label, and the one with a randomized trial of its own.
- SYN-AKE — the third expression-line peptide, aimed at the muscle rather than the nerve.
- The Ordinary Multi-Peptide + HA Serum: the formula — where the two sit, fourth and fifth.
- Peptides for wrinkles — what the category's trials measured, and how.
Sources
- PubChem CID 10099522 — pentapeptide-18, synonyms Leuphasyl and [D-Ala2]leucine-enkephalin, read 2026-09-21.
- Pawłowska M, Marzec M, Jankowiak W, Nowak I. Retinol and oligopeptide-loaded lipid nanocarriers as effective raw material in anti-acne and anti-aging therapies. Life (Basel) 2024;14(10):1212.
- Pawłowska M, Marzec M, Jankowiak W, Nowak I. Solid lipid nanoparticles incorporated with retinol and pentapeptide-18 — optimization, characterization, and cosmetic application. Int J Mol Sci 2024;25(18):10078.
- Akhan D, Bicak B, Kurtur OB, et al. Integrative in silico and in vitro evaluation of Vialox and Leuphasyl pentapeptides for antiaging applications. Chem Biodivers 2026;23(5):e02546.
- Akhan D, Bicak B, Akalin E, Gunduz SK. Pentapeptide-18 as an anti-aging candidate: spectroscopic characterization and molecular interaction analysis. Comput Biol Chem 2026;123:108952.
- Akhan D, et al. In vitro and in silico assessment of anticancer activity of venom-derived and biomimetic neurotransmitter inhibitor pentapeptides. Cell Biochem Biophys 2026.
- Park J, Jung H, Jang B, et al. D-tyrosine adds an anti-melanogenic effect to cosmetic peptides. Sci Rep 2020;10(1):262.
- Bjerke DL, Li J, Gao Y, et al. A framework for the safety evaluation of peptides in cosmetics. Curr Res Toxicol 2026;10:100291.
- Bos JD, Meinardi MMHM. The 500 Dalton rule. Exp Dermatol 2000.
- PubMed counts run 2026-09-21 via NCBI E-utilities, validated against a control query (retinol, randomized controlled trial publication type: 915).