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Cosmetic & skin

Argireline (Acetyl Hexapeptide-8)

Acetyl Hexapeptide-8Acetyl Hexapeptide-3ArgirelineArgireline acetateAc-EEMQRR-NH2INCI: Acetyl Hexapeptide-8

Argireline (Acetyl Hexapeptide-8) is a synthetic topical cosmetic peptide modeled on the N-terminus of SNAP-25 that is studied for its proposed inhibition of SNARE-mediated acetylcholine release; it is a cosmetic ingredient, not a drug.

Sequence fingerprint

EEMQRR

  • Nonpolar1
  • Polar1
  • Acidic (−)2
  • Basic (+)2
  • 6 residues

Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (acetylated N-terminus, amidated C-terminus)

Overview

Argireline is the trade name (originally Lipotec, now Lubrizol) for Acetyl Hexapeptide-8 (formerly designated Acetyl Hexapeptide-3), a synthetic six-residue peptide with the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (one-letter EEMQRR), N-terminally acetylated and C-terminally amidated. Its molecular formula is C34H60N14O12S (average molecular weight ~889 Da), and it carries CAS number 616204-22-9. It is supplied as a water-soluble white powder and is most commonly sold as a dilute aqueous trade solution.

Mechanism (as described in the literature). The peptide is patterned on the N-terminal segment of SNAP-25, a protein in the SNARE complex that mediates Ca2+-dependent neurotransmitter (acetylcholine) exocytosis at the neuromuscular junction. By mimicking SNAP-25, it is reported to interfere with SNARE ternary-complex assembly and thereby reduce acetylcholine release, the proposed basis for a topical, reversible reduction in fine expression-line appearance. Because it shares part of the SNAP-25 target with botulinum toxin, it is sometimes marketed as a "Botox in a bottle," but it is far less potent, is not injected, and is not a substitute for botulinum toxin.

Evidence and limitations. Supporting data come from small cosmetic and in vitro studies; clinical significance is limited by inconsistent measurement methods and, critically, by poor skin penetration — a published study found that under ~0.2% of an applied dose crossed the stratum corneum within 24 hours. Reported safety is favorable in cosmetic use (no serious adverse effects; lower toxicity than botulinum toxin).

Regulatory status. Acetyl Hexapeptide-8 is a cosmetic ingredient (INCI: Acetyl Hexapeptide-8), reviewed by the U.S. Cosmetic Ingredient Review for topical cosmetic use at low leave-on concentrations (up to ~0.005%). It is not an FDA-approved drug and is not a licensed medicine.

Note: Acetyl Hexapeptide-8 should not be confused with SNAP-8 (INCI Acetyl Octapeptide-3 / Acetyl Glutamyl Heptapeptide-1; CAS 868844-74-0), a longer, related octapeptide (Ac-EEMQRRAD-NH2) with its own identity.

Mechanism, evidence & status

A synthetic hexapeptide patterned on the N-terminal segment of SNAP-25 (residues ~12-17), a component of the SNARE complex that mediates neurotransmitter exocytosis. By mimicking native SNAP-25, it is described in the literature as inhibiting SNARE ternary-complex assembly and thereby reducing Ca2+-dependent acetylcholine exocytosis, which is the proposed basis for diminished muscle contraction. Effects are reported as partial and reversible and are constrained by limited skin penetration of the peptide.

Human evidence
Limited; small cosmetic/in vitro studies, marketed cosmetic ingredient
Regulatory status
Marketed as a cosmetic ingredient (INCI: Acetyl Hexapeptide-8), trade name Argireline (developed by Lipotec, now owned by Lubrizol). Reviewed by the Cosmetic Ingredient Review (CIR) for topical cosmetic use. NOT an FDA-approved drug and not a licensed medicine; sold over the counter in cosmetics.
Research applications
  • Studied as a topical cosmetic active for the appearance of expression lines (e.g., periorbital/forehead) in formulation and skin-permeability research.
  • Used as a model peptide for investigating SNARE-complex / SNAP-25 interactions and Ca2+-dependent exocytosis inhibition in vitro.
  • Examined in cosmeceutical delivery research aimed at improving transdermal penetration of large hydrophilic peptides.
Safety considerations
  • The Cosmetic Ingredient Review (CIR) assessed Acetyl Hexapeptide-8 for use in cosmetics; per its 2020 Scientific Literature Review, reported maximum leave-on use concentration is up to ~0.005% (e.g., eye lotions, face/neck products), while formulated trade solutions are supplied at higher strength (commonly 0.5 g/L, i.e., 0.05% aqueous). (cir-safety.org)
  • Skin penetration is limited for a peptide of this size; a published study indicated less than ~0.2% crossed the stratum corneum within 24 hours, which constrains any biological effect. (en.wikipedia.org)
  • Published cosmetic literature reports no serious adverse effects and lower potency and toxicity than botulinum toxin, with mild, reversible action. (pmc.ncbi.nlm.nih.gov)
  • Not a substitute for botulinum toxin; marketing terms such as 'Botox in a bottle' overstate the demonstrated effect, and it is not approved for any medical or injectable use.
References
  1. [1]PubChem Compound: Argireline acetate / Acetyl Hexapeptide-8 (CID 11228338)PubChem
  2. [2]Acetyl hexapeptide-8 - WikipediaWikipedia
  3. [3]Public Interest in Acetyl Hexapeptide-8: Longitudinal Analysis (JMIR Dermatology, 2024)PMC / NCBI
  4. [4]Safety Assessment of Acetyl Hexapeptide-8 and Acetyl Hexapeptide-8 Amide as Used in Cosmetics (CIR, 2020)Cosmetic Ingredient Review