Acetyl Hexapeptide-3 (Argireline)

Also known as: Argireline, Acetyl Hexapeptide-8, Acetyl Hexapeptide-8 Amide, Ac-EEMQRR-NH2, AH8

Evidence: Clinical

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Overview

Synthetic acetylated hexapeptide (Ac-EEMQRR-NH2) modelled on the SNAP-25 N-terminus; a 2013 placebo-controlled trial (n=60) found less periorbital wrinkling after 4 weeks of topical use.

Argireline (acetyl hexapeptide-3, now INCI acetyl hexapeptide-8) was designed by a Spanish academic and industry group as a topical alternative to botulinum toxin; an O/W emulsion reduced wrinkle depth up to 30% in 30 days in healthy women (Blanes-Mira et al., 2002). Independent trials followed: a randomized placebo-controlled study in 60 Chinese adults found 48.9% global improvement in periorbital lines versus 0% on placebo (Wang et al., 2013), and a four-arm study (n=24) found reduced roughness (Raikou et al., 2017). An FDA lab found only 0.01% of an applied dose in the epidermis of human skin in vitro and none in the dermis (Kraeling et al., 2015), so whether it reaches muscle is unproven.

Benefits

Periorbital wrinkle reduction (human RCT, n=60), skin roughness reduction (small human RCT), neurotransmitter release inhibition (in vitro)

Dosing reference

Research dose: Topical only. Published studies used an emulsion stated as 10% (Blanes-Mira 2002); the CIR panel found it safe in cosmetics up to 0.005% and data insufficient above that. No oral or injectable dose exists.

Topical cream or serum applied to expression lines. Trials ran 4 weeks to 60 days, twice daily. Concentration conventions differ: papers state 10% emulsions, while the CIR safety review covers use up to 0.005% peptide.

Mechanism

Proposed. The peptide copies the N-terminal sequence of SNAP-25 and in cell assays interfered with formation or stability of the SNARE complex, inhibiting calcium-dependent neurotransmitter release with potency similar to botulinum toxin A but much lower efficacy (Blanes-Mira et al., 2002). Whether topical application reaches the neuromuscular junction is unresolved: in human and guinea pig skin in vitro almost all peptide stayed on the surface or in the stratum corneum, with none detected in the dermis (Kraeling et al., 2015).

Evidence

Clinical: at least one published human trial or an approved drug

Wrinkle depth fell up to 30% after 30 days of an O/W emulsion in healthy women; cell work showed SNARE complex interference (Blanes-Mira et al., 2002)
Randomized placebo-controlled trial, 60 Chinese adults, twice daily for 4 weeks: 48.9% global improvement in periorbital lines vs 0% on placebo, roughness reduced on silicone replicas (Wang et al., 2013)
Four-arm randomized study (n=24) over 60 days: acetyl hexapeptide-3 reduced roughness and transepidermal water loss vs no peptide (Raikou et al., 2017)
Randomized double-blind pilot in 24 blepharospasm patients: topical use alongside botulinum toxin gave a non-significant trend to longer symptom control, 3.7 vs 3.0 months (Lungu et al., 2013)
Human-trial status: small topical RCTs only, the first from the developers; no injectable study exists, and one Mycobacterium abscessus infection followed off-label facial injection (Chen et al., 2021)

References

Side effects

No significant adverse events in the 24-patient blepharospasm RCT (Lungu et al., 2013); no oral toxicity or primary irritation at high doses in developer tests (Blanes-Mira et al., 2002). Cytotoxic to cultured human cells only far above use levels (Grosicki et al., 2014). The CIR panel found data insufficient above 0.005%. One Mycobacterium abscessus abscess followed facial injection (Chen et al., 2021). Commonly reported (anecdotal): mild stinging or redness.

Storage

Storage: Room temperature, away from light
Lyophilized: 2 years at room temp
Reconstituted: N/A (ready to use)

Pharmacology

Half-life: No published pharmacokinetic data in any species
Bioavailability: Topical (human cadaver skin in vitro, 10% O/W emulsion, 24 h): 0.22% of dose in stratum corneum, 0.01% in epidermis, none in dermis or receptor fluid
Molecular weight: 888.99 Da
Sequence: Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2