What is “Pentapeptide-18” and what is its use?

Pentapeptide-18, also known as Leuphasyl, is a biomimetic peptide developed to specifically target expression wrinkles. Used in numerous facial care products, it belongs, along with argireline, of the new generation of neurocosmetic active ingredients formulated to target the underlying mechanisms responsible for dynamic lines. Designed for topical application, unlike botox with which it is sometimes compared, pentapeptide-18 easily integrates into creams or serums dedicated to the entire face or the eye contour, an area where repeated micro-contractions gradually leave their mark.

Pentapeptide-18 acts by modulating neuromuscular communication involved in facial muscle contractions. Its mechanism of action is inspired by enkephalins, endogenous neuropeptides capable of attenuating nerve transmission. Specifically, pentapeptide-18 binds to enkephalin receptors on the surface of nerve cells, influencing the release of acetylcholine into the synaptic cleft. Acetylcholine is essential for triggering muscle contraction. By partially reducing its release, pentapeptide-18 diminishes the intensity of the repeated micro-contractions responsible for expression wrinkles.

A clinical study evaluated the efficacy of pentapeptide-18 on wrinkles by testing three formulations containing three concentrations: 0.5%, 1%, and 2%. Twenty volunteers applied the formulations daily for two months while wrinkle reduction was measured using a Pro-Derm Analyzer imaging device. The results show that only the 2% concentration achieved a significant improvement, thereby establishing a threshold concentration. The study also highlights one essential point: for neurotransmitter peptides to be effective, application must be made across all muscle areas involved in facial expressions, not just on visible wrinkles.

Recent research has highlighted an additional property of pentapeptide-18 when modified by adding a terminal D-tyrosine: the ability to reduce melanin synthesis. D-tyrosine is already known to inhibit tyrosinase activity, an enzyme essential for melanogenesis, but these studies show for the first time that this effect can be preserved and even optimized when incorporated into a short peptide. The D-tyrosine–enriched pentapeptide-18 thus reduced melanin content and tyrosinase activity in human melanocytes, as well as in MNT-1 melanoma cells, more effectively than D-tyrosine alone. This action was also observed in a human skin model, where the peptide slowed UV- or α-MSH–induced pigmentation, α-MSH being a hormone that stimulates melanogenesis. Clinical studies are nevertheless still required to confirm the depigmenting properties of this peptide.

What is the safety profile of pentapeptide-18?

Pentapeptide-18 is regarded as a safe active ingredient in the scientific literature, with an excellent tolerance profile. The available studies, whether investigating its application at various concentrations, on different facial areas, or over multi-week follow-ups, report no skin irritation, allergic reactions, or serious adverse effects. However, as with any cosmetic ingredient, the precautionary principle applies. Therefore, we recommend performing a skin patch test before first use, to ensure that your skin tolerates both the active ingredient and the overall formulation.

• ANDREI F. & al. The efficiency and safety of leuphasyl – A botox-like peptide. Cosmetics (2014).

• MORAES C. & al. Bioactive peptides: Applications and relevance for cosmeceuticals. Cosmetics (2018).

• BOLLU P. C. & al. Acetylcholine. Neurochemistry in Clinical Practice (2022).

• CIURBA A. & al. Peptides: Emerging candidates for the prevention and treatment of skin senescence: A review. Biomolecules (2025).