Leuphasyl
Pentapeptide-18
Skin & Hair
CAS
64963-01-5
Molecular Weight
570
Da
Human RCT
A Lipotec-developed cosmeceutical pentapeptide that mimics enkephalin activity to dampen nerve signaling at the neuromuscular junction, reducing expression-driven wrinkle depth. Best-evidenced in combination with Argireline (marketed as Argirelox), where the two compounds target the same acetylcholine pathway at distinct binding sites for a synergistic effect. Human evidence exists but is thin and developer-dependent.
Topical · Serum
Intranasal Suitable
No
OTC Supplement
Community Signal
Leuphasyl surfaces rarely as a standalone discussion topic in peptide communities, it's almost always mentioned in the context of Argireline or the Argirelox combination. Skincare forums reference it as a legitimate ingredient with a coherent mechanism, but community consensus generally mirrors the evidence: Argireline is the better-studied compound, and Leuphasyl earns its place primarily in combination formulations rather than as a solo active. No notable safety anecdotes in community discussion.
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What It Is
Leuphasyl is a synthetic five-amino-acid peptide developed by Lipotec (now Lubrizol) as a topical anti-wrinkle active. Its sequence is derived from the endogenous enkephalin neuropeptides, naturally occurring opioid peptides that modulate pain and nerve transmission in the central and peripheral nervous systems. Leuphasyl is designed to mimic this enkephalin activity at the skin surface, targeting the same neuromuscular pathway as Argireline but via a distinct receptor mechanism, which is the basis for their reported synergistic combination.
Mechanism of Action
Leuphasyl binds to enkephalin receptors on nerve terminals in the skin, triggering a cascade that downregulates neuronal excitability and reduces acetylcholine release into the synaptic cleft. Acetylcholine is the neurotransmitter responsible for triggering muscle fiber contraction; by reducing its availability, Leuphasyl attenuates repeated micro-contractions of facial expression muscles, the contractions that gradually deepen expression lines around the eyes, forehead, and mouth. This is mechanistically distinct from how Argireline works. Argireline interferes with the SNARE protein complex (the docking machinery that releases neurotransmitter vesicles), while Leuphasyl acts upstream at the receptor level. Used together, they inhibit the same pathway at two sequential steps, which in vitro and small human studies suggest produces a larger combined effect than either alone.
Use Cases
Topical anti-wrinkle treatment targeting expression lines (forehead, periorbital, perioral)
Combination with Argireline in the Argirelox formulation for enhanced effect
Anti-aging serums and eye creams seeking a botulinum toxin-adjacent mechanism without injection
Known Risks
As a topically applied peptide, Leuphasyl has a favorable safety profile in available studies, no serious adverse events have been reported. The primary limitation is incomplete evidence, not a documented harm signal. Systemic absorption through intact skin is minimal. No published long-term safety studies exist for extended daily use beyond the 28-day trial windows studied.
Available Forms
Leuphasyl is available exclusively as a topical ingredient, no injectable or oral formulations are commercially available or studied. It is incorporated into cosmeceutical serums, anti-aging creams, and eye contour products, typically at concentrations of 0.05–1% (as the Leuphasyl solution, which is itself a dilution of the pure peptide). It is commonly sold as the Argirelox combination blend (Leuphasyl + Argireline in a 1:1 ratio) by cosmetic ingredient suppliers. Pure peptide powder is available from research chemical suppliers.
Regulatory Status
Leuphasyl is classified as a cosmetic ingredient globally and is not subject to drug regulation in the US, EU, or other major markets. As a topical cosmeceutical peptide, it falls under FDA cosmetic regulations (not drug approval), meaning efficacy claims are limited and no pre-market approval is required. It is on the EU Cosmetic Ingredient Database. There are no compounding pharmacy or prescription pathways for this compound. No regulatory agency has evaluated or approved it as a therapeutic drug.
Sources
https://pubmed.ncbi.nlm.nih.gov/19570099/
https://pubmed.ncbi.nlm.nih.gov/33195061/
https://pubmed.ncbi.nlm.nih.gov/41722287/
Similar Compounds
Argireline, Syn-Ake, SNAP-8
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