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

Pentapeptide-18, also known as Leuphasyl, is a biomimetic peptide developed to specifically target expression lines. Used in numerous facial treatments, it forms part, alongside argireline, of the new generation of neurocosmetic active ingredients formulated to act as close as possible to the 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 neural transmission. Specifically, pentapeptide-18 binds to enkephalin receptors on the surface of nerve cells, influencing the release of acetylcholine into the synaptic cleft. This neurotransmitter is essential for triggering muscle contraction. By partially reducing its release, pentapeptide-18 decreases the intensity of the repeated micro-contractions responsible for expression lines.

A clinical trial assessed the efficacy of pentapeptide-18 on wrinkles by testing three formulations at concentrations of 0.5%, 1% and 2%. Twenty volunteers applied the formulations daily for two months, while wrinkle regression was measured using a Pro-Derm Analyser imaging device. The results indicated that only the 2% concentration yielded a significant improvement, thereby setting a threshold concentration. The study also emphasises a key point: for neurotransmitter peptides to be effective, application must be across all the muscle areas involved in facial expressions, rather than solely on the visible wrinkles.

Recent work has highlighted an additional property of pentapeptide-18 when modified by the addition of a D-tyrosine at its terminal position: the ability to reduce melanin synthesis. D-tyrosine is already known to inhibit tyrosinase activity, an enzyme essential for melanogenesis, but this research shows for the first time that this effect can be retained, and even optimised, 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 inhibited UV- or α-MSH-induced pigmentation. However, clinical studies are still required to confirm the depigmenting properties of this peptide.

What is the safety profile of pentapeptide-18?

Pentapeptide-18 is considered a safe active ingredient in the scientific literature, with an excellent tolerance profile. Available studies—whether examining its application at different concentrations, across various facial areas or in follow-ups over several weeks—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 patch test before first use, to ensure that your skin tolerates both the active and the product as a whole.

• 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).