Enkephalin-like peptide · cosmetic
A five-amino-acid synthetic peptide (tyrosine, D-alanine, glycine, phenylalanine, leucine) used in anti-wrinkle creams under the trade name Leuphasyl. It is an analog of leu-enkephalin, one of the body's own opioid peptides. It is marketed as a topical cosmetic ingredient aimed at expression lines, not as a drug.
Expression lines form partly because small facial muscles contract again and again. Chemically, pentapeptide-18 is [D-Ala2]-leucine-enkephalin1. It is described as a neurotransmitter-inhibiting peptide: like natural enkephalins, it is thought to act on nerve cells to dampen their activity and the chemical signals they release, which one paper describes as less release of acetylcholine, the messenger that tells muscles to contract2,3. Less signal should mean less contraction and softer lines, which is why it is often called a Botox-like peptide3. Published human data showing that it crosses intact skin and reaches those nerve endings in meaningful amounts are lacking, and most mechanistic work comes from cell and computer-modeling studies4.
Evidence is thin and mostly preclinical. Computer-modeling and cell studies have explored how the peptide might bind skin-aging targets such as collagen-degrading enzymes, and found no toxicity to cultured human skin cells at the concentrations studied4. A laboratory study that added a D-tyrosine to the peptide reported reduced melanin production in pigment cells and in a 3D human skin model, an ability the unmodified peptide lacked in that work3.
In people, an eight-week study had 20 women each use two night creams: one with lipid nanoparticles carrying retinol and pentapeptide-18, and the same base cream without them. Wrinkle measures improved with the first cream but not the base; because retinol was in the same particles, the change cannot be credited to the peptide2. A PubMed search found no placebo-controlled human trial of the peptide on its own.
Not approved as a drug by the FDA or any other regulator. It is used as a cosmetic ingredient and appears on some US over-the-counter product labels as an inactive ingredient, not as the active drug. Under US law, a claim to change the body's structure or function would make a product a drug5.
No drug-style adverse-effect data exist. In the one small human study of a cream containing it, the authors reported that the lipid nanoparticles reduced the irritation usually seen with retinol, but effects of the peptide itself were not reported separately2. Absorption into the body after skin application has not been measured in published studies, and long-term human data are lacking.
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