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SYN-AKE

Also known as Dipeptide diaminobutyroyl benzylamide diacetate, Syn-Ake, Waglerin-1 mimetic, CAS 823202-99-9

Topical synthetic mimic of a snake venom peptide, intended to block muscle nicotinic acetylcholine receptors.

preclinical Skin & cosmetic cosmetic ingredient

At a glance

Category
Skin & cosmetic
Status
cosmetic ingredient
Route
topical, in a cream, serum or emulsion
Half-life
Not applicable for topical use; systemic absorption is negligible and has not been measured. A 2026 safety-evaluation framework for cosmetic peptides concludes that topically applied peptides of this kind are not expected to reach the bloodstream or lymphatic fluid at all 5
Onset
Supplier panels report change after 28 days of twice-daily use
Molecular weight
approximately 496 g/mol as the diacetate salt (free base approximately 375 g/mol)
Sequence
Not a conventional peptide sequence: a synthetic diaminobutyroyl dipeptide benzylamide, supplied as the diacetate salt. Free base C19H29N5O3; the diacetate salt is reported at approximately 496 g/mol

SYN-AKE is a trade name (originally Pentapharm, now DSM-Firmenich) for the cosmetic ingredient dipeptide diaminobutyroyl benzylamide diacetate 4. It is a cosmetic ingredient, not a medicine: it has no registered indication and no medicines authority has assessed its efficacy. It is applied topically only. Despite the marketing framing, it contains no snake venom — it is a fully synthetic small molecule modelled on part of one.

Doping status: Not listed by WADA

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

Mechanism of action

SYN-AKE was designed as a small-molecule mimic of the active region of waglerin-1, a 22-amino-acid peptide from the venom of the Temple viper (Tropidolaemus wagleri). Waglerin-1 itself is a genuinely characterised pharmacological tool: it is a competitive antagonist at the muscle-type nicotinic acetylcholine receptor and binds with marked selectivity to the alpha-epsilon subunit interface of the adult receptor, an effect mapped in detail in peer-reviewed work on receptor residues 1.

The cosmetic claim is that the synthetic mimic reproduces this antagonism: a peer-reviewed review describes it as a reversible antagonist of muscular nicotinic acetylcholine receptors that prevents acetylcholine from binding 4, so that contraction of the facial mimic muscles is reduced and with it the repeated folding of the skin that produces expression lines. The intended effect is therefore postsynaptic, unlike argireline and SNAP-8, which are presynaptic and act on SNARE-mediated vesicle fusion.

The gap in this reasoning is the same as for the other so-called neurocosmetic peptides, and arguably wider. The neuromuscular junctions of the mimic muscles sit well below the epidermis and dermis; there is no published measurement showing that a topically applied molecule of this size and polarity reaches them in a concentration approaching the one at which receptor blockade occurs in an isolated preparation. The one comparable published figure, for the cosmetic peptide acetyl hexapeptide-8, is 0.22 percent of an applied dose reaching the stratum corneum and 0.01 percent the viable epidermis 5 — and the epidermis is two layers above the muscle. Blockade demonstrated on an isolated muscle preparation does not establish that anything comparable happens through intact skin.

What the research shows

The receptor pharmacology of the natural template, waglerin-1, is well established in independent research. The cosmetic ingredient itself is not: the efficacy figures quoted for SYN-AKE, including a frequently repeated claim of roughly 50 percent wrinkle reduction in 28 days, come from the raw material supplier's dossier and not from independent peer-reviewed research. No randomised controlled trial of this ingredient has been published.

Research in humans

There are no published independent randomised, placebo-controlled clinical trials of SYN-AKE. What circulates are supplier panel studies, typically twice-daily application of a formulation containing 4 percent of the trade solution for 28 days, reporting wrinkle depth reductions in the region of 50 percent. Those protocols have not been peer-reviewed or externally verified, and the figures are far above what independent observers report for topical peptides generally. A 2026 systematic review and meta-analysis of peptides for skin ageing found only two topical peptide trials of adequate quality in the entire field; none concerned this ingredient 3.

Animal and lab research

No animal studies of the cosmetic ingredient. The mechanistic basis rests on in-vitro work with the natural template waglerin-1 on isolated muscle preparations and on receptor binding studies, plus supplier in-vitro data reporting up to roughly 80 percent inhibition of muscle contraction. Those experiments deliver the compound directly to the receptor and say nothing about topical delivery.

Caveats. The critical weakness is that all efficacy data come from the seller, without published protocols, verified blinding or independent replication. The unresolved question of whether the molecule reaches the neuromuscular junction through intact skin has never been addressed in a published study. Marketing that compares this ingredient to botulinum toxin has no published support: botulinum toxin is injected directly into muscle and acts enzymatically and irreversibly, which is not comparable in either potency or route.

What it is used for

  • Topical products aimed at expression lines, especially the glabellar lines between the eyebrows and forehead lines
  • Often formulated together with argireline, SNAP-8 or matrixyl on the assumption that presynaptic and postsynaptic mechanisms combine; the number of distinct peptide combinations in marketed anti-ageing products rose by 88.5% between 2011 and 2018 2
  • Marketed as a topical alternative to injectable neuromodulators — a comparison the available data do not support. The frequently repeated figure of roughly 52 percent reduction in wrinkle visibility over 28 days is reported in review articles 4 but originates in supplier panel data, and a 2026 systematic review of randomised trials of peptides in skin ageing found no trial of this ingredient 3

Dosing

Dose
The trade solution is typically used at 3 to 5 percent of the finished formulation; the content of pure active is far lower, in the parts-per-million range
Frequency
Applied once to twice daily to clean skin
Route
topical — this is a cosmetic ingredient, not an injectable peptide
Duration
Supplier panels ran 28 days; 8 to 12 weeks is a more realistic assessment window. Any effect stops when use stops
  • This is emphatically not an injectable. Injecting a cosmetic peptide solution has never been studied in humans, and cosmetic trade solutions are not sterile and not pyrogen-free.
  • The concentrations named come from supplier formulation documentation, not from clinical dose-finding research.
  • A label claim of '4% SYN-AKE' refers to the trade solution and not to the active substance.
  • Because the mechanism is claimed to be receptor blockade at a neuromuscular junction, the theoretical concern about systemic exposure is worth stating even though absorption is thought negligible: no pharmacokinetic study in humans exists to confirm that.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Reconstitution

Vial sizes
Trade form: an aqueous solution of the active, supplied in bulk to formulators; the raw powder is also sold
Solvent
water or the aqueous phase of an emulsion; not bacteriostatic water for injection — this ingredient is not reconstituted for injection
Storage
Store cool and dark, preferably 2-8 °C for the raw material. A finished aqueous product requires a proper preservative system.

Worked example

For a home or small-batch formulation, the trade solution is added at roughly 3 to 5 percent of total weight to the cooled water phase, with the pH then set to approximately 5 to 6.

Add below approximately 40 °C. Avoid strongly acidic or strongly alkaline phases; stability data outside a pH of roughly 4 to 7 are not published.

Safety

Side effects

  • Generally well tolerated topically; cosmetic peptides as a class perform well in standard skin and eye irritation testing 5
  • Mild redness, tingling or itching at the application site
  • Contact allergy is rare — peptides are typically not electrophilic and so lack the reactivity that drives delayed-type hypersensitivity 5; reactions are more often to preservatives or fragrance in the same product
  • Irritation if applied too close to the eyelid margin or to mucous membranes
  • Long-term safety data are absent; the absence of reported problems reflects the absence of study as much as anything else

Do not use if

  • Known hypersensitivity to the ingredient or to the formulation
  • Damaged, inflamed or freshly treated skin, for example after a peel or laser treatment
  • Do not apply to mucous membranes or in the eyes
  • Injecting this ingredient has never been studied in humans, and cosmetic trade solutions are not sterile or pyrogen-free — a real infection and pyrogen risk. For a compound whose claimed mechanism is neuromuscular receptor blockade, deliberate injection is additionally unwise on pharmacological grounds
  • Pregnancy and breastfeeding: no specific research, although systemic exposure from topical use is expected to be negligible — topically applied cosmetic peptides are not expected to reach the bloodstream or lymphatic fluid 5

Interactions

No systemic drug interactions are expected with topical use, because a topically applied cosmetic peptide is not expected to reach the systemic circulation at all 5 — though this has not been measured for this ingredient specifically. Within a formulation the active is sensitive to extreme pH and to high electrolyte concentrations. Concurrent use with retinoids or exfoliating acids increases the chance of irritation without any demonstrated change in the active's behaviour.

Sources