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PeptideAI
In vitro onlyskin

Syn-Ake

A synthetic mimic of temple viper venom that blocks the muscle-type nicotinic acetylcholine receptor, working on the receiving side of the junction instead of the nerve side.

Also known as Dipeptide Diaminobutyroyl Benzylamide Diacetate, waglerin-1 mimetic, beta-Ala-Pro-Dab-NH-benzyl diacetate, SYN-AKE

In vitro only — Cell or tissue studies. A mechanism, not yet an effect in a living body.

The waglerin-1 pharmacology is real venom science; Syn-Ake's cosmetic performance rests entirely on supplier in-vitro assays and small uncontrolled panels. No independent human trial exists.

How it works

Waglerin-1 is a peptide from the venom of Tropidolaemus wagleri, the temple viper, that binds the epsilon subunit of the adult muscle-type nicotinic acetylcholine receptor with high selectivity and causes flaccid paralysis. Syn-Ake is a much smaller synthetic dipeptide designed to reproduce the active pharmacophore of that toxin in a cosmetically usable molecule. Because it works postsynaptically, it is mechanistically complementary to Argireline and SNAP-8 rather than duplicative. The affinity of the dipeptide is orders of magnitude below native waglerin-1, and it is applied to skin rather than injected into muscle, so the practical effect size is small.

Targets: Muscle-type nicotinic acetylcholine receptor (epsilon subunit), Postsynaptic neuromuscular transmission

Dosing

ProtocolDoseFrequencyRoute
Standard expression-line serumMorning and night on clean skin.—twice dailytopical
  • · Trade solution used at 4-8% of the formula. From raw powder, target 0.01-0.05% w/w — the diacetate is potent enough at low concentrations and expensive at high ones.

Cycling

Continuous use.

Work out your exact syringe units →

Pharmacology

Half-life
Not established.
Onset
Manufacturer panels report wrinkle changes over 28 days of twice-daily use.
Routes
topical
Molecule
Synthetic dipeptide benzylamide, diacetate salt
Sequence length
2 amino acids
Molecular weight
495.6 Da

Handling

Diluent
Distilled or deionised water
Typical mix
20 or 50 mL
Vial sizes
50, 100, 200 mg
Lyophilised
Sealed, cool and dry; freezer for long-term.
Reconstituted
Refrigerated and preserved.

Mixing

Water soluble as the diacetate salt.

Side effects

  • uncommonIrritation or stinging

Do not use if

  • Myasthenia gravis or any neuromuscular junction disorder — the theoretical mechanism is exactly wrong for that population, even if topical exposure is trivial.

Combining it

  • synergyargireline — Pre- and post-synaptic blockade of the same junction.
  • synergysnap-8 — Same complementary logic.
  • redundantvialox — Both are postsynaptic nicotinic receptor antagonists — same target.

What to monitor

  • · Expression-line photographs at 0 and 8 weeks.

Legal status

Cosmetic ingredient (INCI Dipeptide Diaminobutyroyl Benzylamide Diacetate) approved worldwide.

References

  • Pennington et al., waglerin peptides as nicotinic acetylcholine receptor antagonists (preclinical)
  • DSM/Pentapharm SYN-AKE technical dossier (other)

Mechanism in depth

The venom science behind this is real and is worth separating cleanly from the cosmetic claim. Waglerin-1 is a 22-residue peptide from Tropidolaemus wagleri, the temple viper. McArdle's group showed in 1999 that it selectively blocks the epsilon form of the muscle-type nicotinic acetylcholine receptor — that is, the adult isoform, which contains an epsilon subunit in place of the fetal gamma subunit. That selectivity is unusual and pharmacologically valuable, and Molles and colleagues at Scripps later mapped exactly which residues at the alpha-epsilon subunit interface confer it, in two separate papers. So there is a properly characterised, structurally mapped venom pharmacology here, with nanomolar potency at the adult muscle receptor and a defined binding site. Syn-Ake is not that molecule. It is a synthetic dipeptide of about 496 Da designed to reproduce the presumed active pharmacophore of a 22-residue toxin. A dipeptide cannot make the same set of interface contacts a 22-residue peptide makes, and the affinity is correspondingly orders of magnitude lower — Pentapharm has never published a Ki for it against the muscle nicotinic receptor. Mechanistically the postsynaptic position is genuinely complementary to the SNARE peptides, which act presynaptically, and that part of the marketing is fair. But blocking the receiving end of a junction you cannot reach is the same problem as blocking the sending end. Recent multi-ingredient clinical work pairing Syn-Ake with acetyl hexapeptide-8 shows measurable wrinkle improvement, but the formulation also contained gluconolactone, niacinamide and laminaria extract, so attribution is impossible.

What usually goes wrong

The myasthenia gravis contraindication in the Core record is theoretical, and I want to be precise about that rather than alarming: topical exposure at 0.01-0.05% is almost certainly irrelevant to a myasthenic. But the mechanism is exactly the wrong direction for that disease, the compound has never been studied in that population, and there is no upside worth the uncertainty. The more common practical failure is the same trade-solution confusion as the rest of this group — the supplier level is 4-8% of a dilute solution, which is roughly 0.01-0.05% actual peptide, and someone formulating from powder to 4% has made something a hundredfold stronger. The third issue is the snake-venom marketing, which sets expectations at a level the dipeptide cannot meet. Waglerin-1 causes flaccid paralysis. Syn-Ake causes, at most, a modest smoothing.

Pharmacokinetics

Metabolism
The benzylamide C-terminus and the non-standard diaminobutyric acid residue both resist normal peptidase processing, which is why a dipeptide survives in a cosmetic formulation at all.
Elimination
No meaningful systemic exposure from topical use.

Receptor targets

  • Muscle-type nicotinic acetylcholine receptor, alpha-epsilon subunit interface — Waglerin-1 itself is nanomolar and epsilon-selective; no affinity has ever been published for the Syn-Ake dipeptide

    Competitive postsynaptic blockade, preventing acetylcholine from depolarising the muscle fibre. Reversible.

  • Adult versus fetal receptor isoform selectivity — The selectivity is a property of native waglerin-1, mapped to specific interface residues

    Pharmacologically elegant in the toxin; unproven to be retained in the cosmetic mimetic.

Trials

  • Zhu et al. clinical and ex vivo evaluation of a serum containing dipeptide diaminobutyroyl benzylamide diacetate with acetyl hexapeptide-8 and gluconolactone (Int J Cosmet Sci) Ex vivo plus two clinical studies · n=50 · 12 weeks · 2026

    35-69% improvement in static wrinkle clinical scoring at 12 weeks (p < 0.001) in 50 subjects; a further 42-subject arm showed 10-13% improvement in dynamic wrinkle scores. Ex vivo biomarker work showed increased elastic and collagen fibres and effects on MMP-1. Multi-ingredient, so the Syn-Ake contribution cannot be isolated.

What to expect, and when

Week 4: manufacturer panels report change at 28 days. Week 12: the timepoint at which the multi-ingredient Zhu serum showed its wrinkle-scoring improvements. Discontinuation: reversal within days to a couple of weeks, as expected for a reversible competitive mechanism.

Stacking and comparisons

Pairs mechanistically with Argireline, SNAP-8 and Leuphasyl — presynaptic plus postsynaptic — and that is the combination in the Zhu 2026 serum that produced the best human numbers this ingredient has. It is genuinely redundant with Vialox, which hits the same postsynaptic receptor; running both is buying the same block twice. No chemical incompatibilities. As a diacetate salt it is water soluble and stable across cosmetic pH. The practical caveat: it is one of the more expensive raw materials in this group and the supplier use level is low, so people who over-concentrate it waste money quickly.

Against Vialox, the same postsynaptic target with a better-characterised parent pharmacology — waglerin-1 has three independent primary papers behind it, curare-mimicry for Vialox has none specific to pentapeptide-3. Against Argireline and SNAP-8, mechanistically complementary rather than competing, and structurally the smallest molecule of the four, which is the only delivery advantage anyone in this group can claim. Against botulinum toxin, no comparison. If you want one topical neuromuscular peptide, Syn-Ake plus Argireline is the pairing with the most human data behind it, which is still not much.

Rough cost

$15–$70/month. Raw material runs roughly $50-120 per gram, among the more expensive in this class, though the use level is very low. Finished products $18-70 a month. Market observation, not a sourced pricing study.

Genuinely uncertain

  • No binding affinity for the Syn-Ake dipeptide at the muscle nicotinic receptor has ever been published. The entire pharmacological claim rests on analogy to waglerin-1.
  • No permeation study of this compound in human skin exists.
  • Every clinical dataset containing it is multi-ingredient, so its individual contribution has never been isolated.
  • Whether the epsilon-subunit selectivity of waglerin-1 is retained in the dipeptide is unknown and, given the size difference, unlikely.
  • The molecular weight of 495.6 Da in the Core record is plausible for the diacetate salt but is unconfirmed against a primary source.

Papers