Acetyl Hexapeptide-8
Acetyl Hexapeptide-8 is the updated INCI name for Argireline (formerly Acetyl Hexapeptide-3), a synthetic SNARE complex inhibitor that reduces neurotransmitter release to attenuate facial muscle contractions and expression lines.
Acetyl Hexapeptide-8 is the current INCI (International Nomenclature of Cosmetic Ingredients) designation for the synthetic hexapeptide previously registered as Acetyl Hexapeptide-3 and commercially known as Argireline. The compound itself is unchanged -- the PCPC (Personal Care Products Council) reassigned the INCI number during a routine nomenclature update.
Overview
The peptide was originally developed by Lipotec (now part of Lubrizol/Berkshire Hathaway) and registered under the INCI name Acetyl Hexapeptide-3. When the PCPC updated the International Cosmetic Ingredient Dictionary and Handbook, the compound was reassigned to Acetyl Hexapeptide-8 to accommodate new entries in the hexapeptide numbering sequence. Both names refer to the identical molecule: an acetylated hexapeptide with the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2.
This nomenclature change has caused confusion in the cosmetics industry, with some products listing the old name and others the new one. Regulatory bodies in the EU (INCI-compliant labeling under EC Regulation 1223/2009) now expect the updated Acetyl Hexapeptide-8 designation on product labels, though Acetyl Hexapeptide-3 remains widely recognized and accepted in practice.
Mechanism of Action
Acetyl Hexapeptide-8 mimics the N-terminal domain of SNAP-25 (Synaptosomal-Associated Protein of 25 kDa), one of three proteins that assemble into the SNARE complex required for synaptic vesicle docking and fusion at the presynaptic terminal. By competing with endogenous SNAP-25 for incorporation into the ternary SNARE complex (SNAP-25 + syntaxin + VAMP/synaptobrevin), the peptide destabilizes complex assembly and reduces the efficiency of vesicular neurotransmitter release.
The mechanism proceeds through several steps:
- SNARE competition: The hexapeptide competes with native SNAP-25 at the N-terminal binding interface
- Complex destabilization: Incomplete SNARE complexes form less efficiently, reducing vesicle fusion probability
- Reduced exocytosis: Acetylcholine release at the neuromuscular junction decreases in a dose-dependent manner
- Attenuated contraction: Facial expression muscles receive weaker signals, reducing dynamic wrinkle formation
Unlike botulinum neurotoxins, which enzymatically cleave SNARE proteins irreversibly, Acetyl Hexapeptide-8 acts as a reversible competitive inhibitor. This fundamental difference underlies its safety profile and suitability for over-the-counter topical use Blanes-Mira et al. (2002).
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Research
Penetration and Delivery
Skin penetration remains the primary challenge for topical peptide delivery. Kraeling et al. (2015) demonstrated measurable skin penetration of Acetyl Hexapeptide-8 from cosmetic formulations using in vitro Franz diffusion cell studies. Nanostructured lipid carriers, liposomal encapsulation, and chemical penetration enhancers have all been shown to improve dermal delivery Wang et al. (2013).
INCI Nomenclature History
The transition from Acetyl Hexapeptide-3 to Acetyl Hexapeptide-8 reflects the PCPC's ongoing effort to maintain a coherent numbering system as new peptide ingredients enter the cosmetic market. The change does not indicate any structural modification, reformulation, or change in regulatory status. Products labeled with either name contain the same active ingredient at the same concentrations.
Formulation Considerations
Acetyl Hexapeptide-8 is typically supplied as a lyophilized powder or aqueous solution at defined concentrations. Standard cosmetic formulations use 5-10% of a commercial solution containing 0.05% active peptide. The peptide is water-soluble, stable at pH 5.0-7.0, and compatible with most cosmetic ingredients. It is heat-sensitive above 40C and should not be added to formulations before cooling.
Safety Profile
The safety profile of Acetyl Hexapeptide-8 is identical to that documented under its previous INCI name. Topical application at concentrations up to 10% of commercial solution is well-tolerated with no significant adverse effects reported. Dermal irritation and sensitization testing show minimal reactivity. No systemic neuromuscular effects have been observed, consistent with limited transdermal absorption. The reversible nature of SNARE complex inhibition provides an inherent safety margin. The peptide is approved for cosmetic use in the EU, US, and other major markets under both legacy and updated INCI designations.
Pharmacokinetic Profile
Acetyl Hexapeptide-8 — Pharmacokinetic Curve
TopicalQuick Start
- Route
- Topical
Molecular Structure
- Formula
- C34H60N14O12S
- Weight
- 888.99 Da
- CAS
- 616204-22-9
- PubChem CID
- 11390410
- Exact Mass
- 221.1528 Da
- LogP
- 0.7
- TPSA
- 70.1 Ų
- H-Bond Donors
- 1
- H-Bond Acceptors
- 3
- Rotatable Bonds
- 3
- Complexity
- 359
Identifiers (SMILES, InChI)
InChI=1S/C12H19N3O/c1-3-8(2)10(14)11(16)15-5-4-9-6-12(9,15)7-13/h8-10H,3-6,14H2,1-2H3/t8-,9+,10-,12+/m0/s1
VFMGPTHTVPHION-MIZYBKAJSA-NResearch Protocols
topical
This fundamental difference underlies its safety profile and suitability for over-the-counter topical use [Blanes-Mira et al. Penetration and Delivery Skin penetration remains the primary challenge for topical peptide delivery.
transdermal Injection
Argireline, as a charged, hydrophilic hexapeptide exceeding this molecular weight threshold, requires formulation strategies that enhance its transdermal flux to reach the target site -- the neuromuscular junctions underlying facial expression muscles.
Interactions
Quality Indicators
What to look for
- Well-established safety profile
Frequently Asked Questions
References (5)
- [6]
- [8]Negari et al Peptide-based cosmeceuticals: mechanisms and clinical applications Int J Mol Sci (2023)
- [3]Wang Y et al Enhanced skin permeation of Argireline through nanostructured lipid carriers J Biomed Nanotechnol (2013)
- [1]Blanes-Mira C et al A synthetic hexapeptide (Argireline) with antiwrinkle activity Int J Cosmet Sci (2002)
- [2]Kraeling MEK et al In vitro skin penetration of acetyl hexapeptide-8 from cosmetic formulations Cutan Ocul Toxicol (2015)
Acetyl Hexapeptide-3 (Argireline)
Acetyl Hexapeptide-3 (Argireline) is a synthetic hexapeptide that inhibits SNARE complex formation, reducing neurotransmitter release and attenuating facial muscle contractions associated with wrinkle development.
Acetyl Tetrapeptide-5
Acetyl Tetrapeptide-5 (Eyeseryl) is a Lipotec-developed peptide that targets undereye puffiness and edema by reducing vascular permeability and inhibiting glycation, researched for periorbital anti-aging applications.