Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
A SNAP-25 fragment mimic: the one cosmetic peptide with a published mechanism, a 30-day wrinkle-depth study, and a stability problem (methionine oxidation) that testing can catch.
Also known as: acetyl hexapeptide-8 · acetyl hexapeptide-3 · Ac-EEMQRR-NH2 · Argireline NP
Part of the Cosmetic & skin peptides cluster
Overview
Argireline (acetyl hexapeptide-8, formerly acetyl hexapeptide-3) is the synthetic acetylated hexapeptide Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, modelled on the N-terminus of SNAP-25, the SNARE protein botulinum toxin cleaves. In cosmetic-science studies a 10% emulsion reduced wrinkle depth by up to 30% over 30 days, and it inhibits neurotransmitter release in vitro with far lower efficacy than the toxin. It is a permitted cosmetic ingredient, not an approved drug.
Source & context
Biological / chemical source: Synthetic acetylated hexapeptide (fragment of SNAP-25)
Primary research or clinical context: Cosmetic ingredient in topical formulations (permitted as a cosmetic in major markets); not an approved drug — two blepharospasm trials did not lead to approval
What Argireline is
Argireline is the trade name for acetyl hexapeptide-8 (originally catalogued as acetyl hexapeptide-3), a synthetic six-residue peptide, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, developed by the Spanish company Lipotec through a rational design programme reported in 2002. Its sequence copies the N-terminal end of SNAP-25, one of the three SNARE proteins whose assembly pulls a neurotransmitter vesicle to the nerve terminal membrane and which botulinum toxin A cleaves. The design idea is a non-toxic molecule that competes with SNAP-25 for the complex and so dampens the muscle signalling that folds expression lines. It is sold in serums and creams worldwide as a cosmetic ingredient.
Sequence and chemistry
In one-letter code the core is EEMQRR, capped with an N-acetyl group and a C-terminal amide (formula C34H60N14O12S for the amide form; about 889 Da). Two glutamates give the N-terminus a negative charge and two arginines give the C-terminus a positive one, which matters for penetration into skin. The methionine at position 3 is oxidisable: Kluczyk et al. (Chemistry & Biodiversity 2021) analysed commercial creams and sera by HPLC-MS/MS and found both Argireline and its oxidised form, identifying the methionine sulfur as the oxidation site and raising the question of how other ingredients affect the peptide's stability in a finished product.
Mechanism: a SNARE mimic, not a toxin
The discovery paper (Blanes-Mira et al., International Journal of Cosmetic Science 2002) showed that Argireline significantly inhibited neurotransmitter release in vitro with a potency similar to botulinum toxin A but, as expected for a non-enzymatic peptide, much lower efficacy. The mechanism proposed is interference with the formation or stability of the SNARE complex required for calcium-dependent exocytosis. Unlike the toxin, the peptide does not cleave anything and does not enter the neuron; its effect is competitive and reversible, and it must reach the neuromuscular junction through intact skin, which is the principal limitation of every topical claim.
Human evidence
The 2002 paper reported that an oil-in-water emulsion containing 10% Argireline reduced wrinkle depth by up to 30% in healthy women after 30 days, measured by skin topography. A 2023 double-blind split-face study of 19 women (Henseler, GMS Interdisciplinary Plastic and Reconstructive Surgery 2023) compared a hyaluronic-acid serum with and without Argireline around the eyes for four weeks using the Visia camera system. A 2013 study reported anti-wrinkle effects in Chinese subjects and collagen changes in aged mice (Wang et al., Journal of Cosmetic and Laser Therapy 2013). These are small cosmetic-endpoint studies, not clinical trials of a medicine. Six trials are registered on ClinicalTrials.gov, including a phase 1/2 and a terminated phase 2 study of acetyl hexapeptide-8 for blepharospasm; neither led to a drug approval.
| Study | Design | Finding |
|---|---|---|
| Blanes-Mira et al. 2002 | 10% emulsion, healthy women, 30 days | Wrinkle depth reduced up to 30% |
| Wang et al. 2013 | Chinese subjects; aged-mouse histology | Anti-wrinkle effect; collagen changes in mice |
| Henseler 2023 | Double-blind split-face, 19 women, 4 weeks | Visia wrinkle scores compared side to side |
| NCT00942851 / NCT01750346 | Phase 1/2 and phase 2, blepharospasm | Completed / terminated; no approval |
Safety and cytotoxicity
The 2002 study reported no oral toxicity in vivo and no primary skin irritation at high doses. Grosicki et al. (Acta Biochimica Polonica 2014) measured antiproliferative effects of Argireline solutions in HEK-293 cells, IMR-32 neuroblastoma cells and primary human skin fibroblasts, calculating IC50 values to fill what they called an evident gap in independent cytotoxicity data. Public interest has risen sharply — search volume for Argireline and “Botox in a bottle” jumped in 2022 (Olsson et al., JMIR Dermatology 2024) — without a corresponding increase in controlled safety or efficacy data.
Argireline vs botulinum toxin
The comparison is built into the marketing, so it is worth stating plainly. Botulinum toxin A is an injected enzyme that cleaves SNAP-25 inside the nerve terminal and blocks muscle contraction for months. Argireline is a topical peptide that competes reversibly with SNAP-25 for complex assembly, with in-vitro potency described as similar but efficacy described as much lower, and that must diffuse through skin to act at all. The published effect is a percentage reduction in measured wrinkle depth in small cosmetic studies, not paralysis of the muscle. The phrase “needle-free Botox” describes the intent of the design, not equivalent performance.
Status and what this page is not
Argireline is a permitted cosmetic ingredient in the US, Canada, the EU and most other markets and is not an approved drug anywhere. This profile describes cosmetic-science literature on the appearance of skin; it makes no medical claim, and it is not a recommendation for any product.
Sequence
One-letter sequence commonly cited for Argireline (educational; isoforms and modifications may differ):
EEMQRR
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 — the N-terminal hexapeptide of SNAP-25, N-acetylated and C-amidated
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass
Reference policy updated: 2026-10-05
- PubChem molecular record · 2026-10-01
- Molecular formula
- C35H62N14O11S
- Average reference mass
- ≈ 887
- Receptors
- No receptor. Proposed to interfere with assembly or stability of the SNARE complex (SNAP-25 / syntaxin / synaptobrevin) that drives Ca2+-dependent vesicle fusion, thereby reducing neurotransmitter release
- Backbone
- Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 — the N-terminal hexapeptide of SNAP-25, N-acetylated and C-amidated
- C-terminus
- Amide
- Status
- Cosmetic ingredient; not an approved drug in any jurisdiction as of September 2026
N-terminal acetyl and C-terminal amide cap both ends. The methionine at position 3 is the molecule's weak point: it oxidises in finished cosmetics, and oxidised Argireline has been detected in commercial creams and sera.
- PubChem CID: 71587772
- CAS RN: 616204-22-9
- UNII: L4EL31FWIL
Chemistry values: curated profile, PubChem · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 6 registered studies with “Argireline” as an intervention (snapshot 2026-09-06). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06143033 | A Clinical Trial to Evaluate the Effects of an Eye Serum on Improving the Appearance of the Periorbital Area | Not applicable | completed | 2024-02-22 |
| NCT03878381 | Investigating the Wrinkle Reduction Potential of a Novel Compounded Skin Care Cream | Early phase 1 | completed | 2022-11-01 |
| NCT02597777 | Topical Acetyl Hexapeptide-8 and the Cosmetic Appearance of Oily Skin | Not applicable | completed | 2017-04-05 |
| NCT01750346 | Acetyl Hexapeptide-8 for Blepharospasm | Phase 2 | terminated | 2016-11-10 |
| NCT00942851 | A Study of Acetyl Hexapeptide-8 (AH8) in Treatment of Blepharospasm | Phase 2 | completed | 2012-09-06 |
| NCT01381484 | Argireline in Treatment of Periorbital Wrinkles | Phase 3 | completed | 2011-06-27 |
Argireline — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 — the N-terminal hexapeptide of SNAP-25, N-acetylated and C-amidatedAverage reference mass: 887 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Argireline
What is Argireline?+
Argireline (acetyl hexapeptide-8, formerly acetyl hexapeptide-3) is the synthetic acetylated hexapeptide Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, modelled on the N-terminus of SNAP-25, the SNARE protein botulinum toxin cleaves. In cosmetic-science studies a 10% emulsion reduced wrinkle depth by up to 30% over 30 days, and it inhibits neurotransmitter release in vitro with far lower efficacy than the toxin. It is a permitted cosmetic ingredient, not an approved drug.
What Canadian product status is recorded for Argireline?+
Canadian product status for Argireline has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Argireline?+
Argireline is commonly described as approximately 6 amino acids (Cosmetic ingredient peptide).
What is Argireline?+
Acetyl hexapeptide-8, a synthetic six-residue peptide (Ac-EEMQRR-NH2) that mimics the N-terminus of SNAP-25 and is used as a topical cosmetic ingredient for the appearance of expression lines.
Does Argireline work?+
In the 2002 discovery study a 10% emulsion reduced wrinkle depth by up to 30% over 30 days in healthy women; later studies are small cosmetic-endpoint trials. It inhibits neurotransmitter release in vitro with far lower efficacy than botulinum toxin.
Is Argireline the same as Botox?+
No. Botulinum toxin is an injected enzyme that cleaves SNAP-25; Argireline is a topical peptide that reversibly competes with SNAP-25 and must pass through skin to act.
Is Argireline safe?+
It is a permitted cosmetic ingredient with no reported irritation or oral toxicity in the discovery study; independent cytotoxicity data are limited to cell-line IC50 measurements.
Why does Argireline degrade in creams?+
Its methionine residue oxidises. Oxidised Argireline has been found in commercial products by HPLC-MS, so formulation and storage affect what is actually on the skin.
Is Argireline approved as a drug?+
No. Two trials of acetyl hexapeptide-8 for blepharospasm were run; one was terminated and neither led to approval.
Further reading
- CategoriesCosmetic Peptides vs Research Peptides: What’s the Difference?GHK-Cu, Matrixyl, SNAP-8 and skincare peptides versus injectable research peptides—regulation, exposure routes, and marketing language.
- Cosmetic peptidesGHK-Cu and Copper Peptides: The Science of Skin and RepairWhat GHK-Cu is, why copper peptides are studied in skin and wound research, and how cosmetic use differs from injectable research claims. An evidence-focused educational explainer.
- FoundationsCollagen Peptides Explained: A Consumer-Friendly GuideA plain-language explainer on hydrolyzed collagen peptides—what they are, collagen types I, II and III, and how these dietary ingredients differ from research peptides. Educational only, not medical advice.
Related peptides
References & further reading
- 1.Blanes-Mira et al. (2002). A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci
- 2.Kluczyk et al. (2021). Argireline: Needle-Free Botox as Analytical Challenge. Chem Biodivers
- 3.Velazco de Maldonado et al. (2023). Polydioxanone Bioactive Sutures-Acetyl Hexapeptide-8 (Argireline): An Intelligent System for Controlled Release in Facial Harmonization. J Cutan Aesthet Surg
- 4.Wang et al. (2013). The anti-wrinkle efficacy of Argireline. J Cosmet Laser Ther
- 5.Chen et al. (2021). Mycobacterium abscessus infection after facial injection of argireline: A case report. World J Clin Cases
- 6.Wyrzykowski et al. (2024). Influence of the modification of the cosmetic peptide Argireline on the affinity toward copper(II) ions. J Pept Sci
- 7.Wang et al. (2013). The anti wrinkle efficacy of synthetic hexapeptide (Argireline) in Chinese Subjects. J Cosmet Laser Ther
- 8.Wang et al. (2013). The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. Am J Clin Dermatol
- 9.Henseler (2023). Investigating the effects of Argireline in a skin serum containing hyaluronic acids on skin surface wrinkles using the Visia Complexion Analysis camera system. GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW
- 10.Grosicki et al. (2014). The study of cellular cytotoxicity of argireline — an anti-aging peptide. Acta Biochimica Polonica
- 11.Olsson et al. (2024). Public Interest in Acetyl Hexapeptide-8: Longitudinal Analysis. JMIR Dermatology
- 12.PubChem — Acetyl hexapeptide-3 (CID 71587772)