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Syn-Ake3 residues (approx.)APKEach bubble = one amino acid. Size = residue mass. Color = chemical class.Uses closest standard amino acids for non-standard residues.Also known as: Tripeptide-3, SYN-AKE, Snake Venom Peptide
In cultured muscle cells, a single tripeptide cut contraction frequency by 82% in two hours. Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate, CAS 823202-99-9) is a synthetic peptide modeled after Waglerin-1 from Temple Pit Viper venom. It blocks the postsynaptic nicotinic acetylcholine receptor, relaxing facial muscles topically instead of through injection. No independent placebo-controlled RCT isolating Syn-Ake in humans has been published yet. The manufacturer's own 45-subject study found up to 52% forehead wrinkle depth reduction at 28 days using a 4% cream. Skincare formulators and anti-aging protocol builders use it as a non-invasive complement to botulinum toxin, often stacked with SNAP-8 for dual neuromuscular coverage.
Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate, Tripeptide-3, CAS 823202-99-9) is a synthetic tripeptide built to mimic Waglerin-1, a paralytic peptide from the Temple Pit Viper (Tropidolaemus wagleri). The manufacturer's own 45-subject study reported 52% forehead wrinkle depth reduction at 28 days with 4% cream. No actual snake venom is involved. DSM-Firmenich synthesizes it chemically, and the compound is vegan-compatible. The mechanism is specific. Syn-Ake binds to the epsilon subunit of the muscular nicotinic acetylcholine receptor at the neuromuscular junction. That binding blocks acetylcholine from triggering muscle contraction. The result: localized relaxation of the frontalis, orbicularis oculi, and corrugator supercilii, the muscles responsible for forehead lines, crow's feet, and frown lines. Unlike botulinum toxin, this binding is fully reversible. Stop applying it and muscle function returns within one to two weeks. The skincare formulator community has adopted a standard stack: 4% Syn-Ake plus 10% SNAP-8 in a hyaluronic acid serum base, applied twice daily. SNAP-8 blocks acetylcholine release presynaptically while Syn-Ake blocks the receptor postsynaptically. The combination covers both sides of the neuromuscular junction. Research status is honest: no independent double-blind placebo-controlled RCT isolating Syn-Ake as a single active exists. The most-cited human study (Trookman 2009)[1] tested a multi-ingredient product funded by SkinMedica. Gok and colleagues confirmed the mechanism and safety profile through in silico and in vitro work [2]. Community experience across formulator forums and skincare subreddits is consistent: effects are real but more modest than Botox, landing around 20 to 30% visible improvement compared to Botox's 80 to 95%.
Syn-Ake is a competitive antagonist of the muscular nicotinic acetylcholine receptor (mnAChR). The tripeptide targets the epsilon subunit of that receptor, sitting in the same binding pocket where acetylcholine normally docks. When Syn-Ake occupies the site, acetylcholine can't trigger sodium ion channel opening. Without sodium influx, the motor endplate doesn't depolarize. Without depolarization, excitation-contraction coupling fails. The muscle relaxes. This differs from botulinum toxin in a key way. Botox irreversibly cleaves SNARE complex proteins on the presynaptic side, stopping acetylcholine vesicle release entirely. Syn-Ake works on the opposite side of the synapse, and its binding is reversible. Once the peptide dissociates from the receptor, normal contraction resumes. That reversibility is both a safety feature and a limitation; the relaxation requires continuous topical application to maintain. In cultured muscle cells, 0.025% Syn-Ake reduced contraction frequency by 36% within one minute and 82% within two hours. Topical onset through intact skin is slower because the peptide must cross the stratum corneum first. At 495.58 Da, Syn-Ake falls just below the 500 Da skin penetration threshold, enabling passive transcorneal diffusion without lipid conjugation. Gok and colleagues [2] identified secondary binding targets through in silico modeling: SIRT1 (a sirtuin deacetylase in cellular longevity pathways) at -9.32 kcal/mol and matrix metalloproteinases MMP-1, MMP-8, and MMP-13. These interactions suggest possible collagen degradation inhibition beyond the primary neuromuscular effect. The peptide also scavenges free radicals in a concentration-dependent DPPH assay.
In vitro evidence for neuromuscular mechanism is strong (82% contraction reduction at 2h, 0.025% concentration, cultured muscle cells). Manufacturer-sponsored 45-subject human study shows 52% forehead wrinkle depth reduction at 28 days (4% cream). No independent, placebo-controlled RCT isolating Syn-Ake contribution in humans exists. The most-cited "clinical" study (Trookman 2009)[1] is industry-funded and tested a multi-ingredient product: efficacy cannot be attributed to Syn-Ake alone. A 2024 nanoemulsion study (PMC11053593) confirmed sebum/pore benefits at 0.012%: a different clinical endpoint. Overall: compelling mechanism, weak isolated human evidence.
DSM-Firmenich manufacturer study: 45 healthy subjects, 4% Syn-Ake forehead cream, up to 52% wrinkle depth reduction at 28 days. Gok et al. 2024 (PMID 37349941): in silico + in vitro anti-aging activity, SIRT1 binding (−9.32 kcal/mol), MMP-13 inhibition, genotoxicity-favorable. Moretto et al. 1999 (PMID 10087048): independent confirmation of epsilon-subunit mnAChR blockade mechanism.
Primary efficacy study is manufacturer-funded and unpublished in peer review. Trookman 2009 (the most-cited human study) tested a multi-ingredient product: cannot isolate Syn-Ake contribution. No independent double-blind placebo-controlled RCT of Syn-Ake as a single active. Nanoemulsion 2024 study tested 0.012% (far below clinical 4%) for a different endpoint (sebum/pore size). No long-term safety or efficacy data (>12 weeks). Skin penetration depth at clinically relevant dermis levels unconfirmed.
Valued by the skincare formulator and DIY community as a non-invasive topical Botox alternative. Results accepted as more modest than Botox; used as a complement or maintenance tool rather than a replacement. SNAP-8 combination at 4% Syn-Ake + 10% SNAP-8 is the benchmark stack. Skepticism centers on manufacturer-funded evidence and the full reversibility of effects.
Both science and community accept the postsynaptic mnAChR mechanism and 4% as the benchmark concentration. Science notes the absence of an independent isolated RCT; community accepts this gap and uses the product empirically, calibrating expectations below Botox. Disagreement is on magnitude of evidence, not mechanism or practical use.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 2mg | Daily |
| Moderate | 4mg | 2x Daily |
| Aggressive | 6mg | 2x Daily |
Syn-Ake is a topical peptide. No reconstitution, no bacteriostatic water, no syringes. You're working with serums and creams, not vials. The most common mistake: buying a product that says "contains Syn-Ake" without listing the actual percentage. Below 3%, efficacy drops off. The manufacturer's clinical data used 4%. Garden of Wisdom sells a verified 7% serum ($28 to $87 depending on size) that's the go-to reference product. For DIY formulators working with raw powder (CAS 823202-99-9, approximately $210 per 200 mg from Cenexal Labs or Peptide.shop): dissolve in a hyaluronic acid serum base. 4 mg per 100 mg of final product gives you 4% w/w. That 200 mg supply makes roughly 5 g of 4% serum, enough for about a month of twice-daily facial application. Apply to clean, dry skin. Not damp. Dampness changes absorption kinetics. Wait two to three minutes before layering moisturizer or SPF. Don't apply within 48 hours of a chemical peel. Store finished serums at 2 to 8 degrees Celsius and use within 6 months of opening.
Apply twice daily for 12 weeks to achieve full wrinkle-reducing effect. Manufacturer studies report significant results at 28 days, with continued improvement through 12 weeks. A 2-week break is optional: no receptor desensitization or tachyphylaxis has been reported with continuous use. The reversible competitive binding mechanism means effects diminish gradually over 1-2 weeks after discontinuation as receptor occupancy decreases. Long-term continuous use is commonly practiced in cosmeceutical regimens.
Syn-Ake has no documented receptor desensitization, tachyphylaxis, antibody formation, or systemic hormonal axis effects requiring cycling. The 12-week-on / 2-week-off schedule used in cosmeceutical practice is derived from the duration of available clinical studies (not pharmacological necessity) and provides a natural reassessment window. Continuous long-term use is widely practiced in the skincare community with no adverse outcomes reported. The reversible competitive binding mechanism means effects dissipate within 1–2 weeks of stopping, providing a natural "off" observation period for users who choose to cycle.
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Expected: Gradual softening of forehead and periorbital expression lines by week 4–6 in responders; peak effect at weeks 8–12. Non-responders apparent by week 8. Manufacturer data: up to 52% wrinkle depth reduction at 4% over 28 days.
Monitor: Photograph expression lines in consistent lighting at baseline, week 4, and week 12. Discontinue if contact dermatitis develops. Verify product's declared % concentration: "contains Syn-Ake" without a stated % likely delivers sub-therapeutic dose.
Syn-Ake absorbs better through dry skin than damp skin.
Dispense a pea-sized amount of 4% Syn-Ake serum onto your fingertip. If using a DIY formulation, confirm your concentration is at least 3 to 4%.
Apply in thin layers to expression-line-prone areas: forehead (frontalis), crow's feet (periorbital region), frown lines (glabella), and around the mouth (perioral area). Use gentle pressing motions rather than rubbing.
Wait 2 to 3 minutes for full absorption before layering other products. The peptide needs direct skin contact time.
In the evening, follow with your standard PM routine (niacinamide, hyaluronic acid, or facial oil are all compatible).
Apply twice daily (AM and PM) for at least 4 weeks before assessing results. Full evaluation requires 12 weeks.
Either use a combined 4% Syn-Ake plus 10% SNAP-8 serum, or layer one immediately after the other before the absorption wait.
Do not apply over freshly botulinum-toxin-injected areas, broken skin, active sunburn, or within 48 to 72 hours of a chemical peel (glycolic acid above 20% or TCA).
Store opened serums at 2 to 8 degrees Celsius, protected from direct light. Stable at pH 5 to 7. Discard after 6 months.
N/A: this is the reference route and concentration
All manufacturer and clinical studies used topical emulsion or cream at 4% concentration. Low MW (495.58 Da, below the 500 Da penetration threshold) enables passive transcorneal diffusion without lipid conjugation requirement.
Much lower active concentration (0.012% in 2024 study vs. 4% standard) with potentially higher local bioavailability due to lipid nanocarrier bypassing aqueous diffusion limitation
PMC11053593 (Pharmaceutics 2024): water-in-oil nanoemulsion of Syn-Ake at 0.012% showed sebum reduction and pore-size benefits in human subjects: a different endpoint than wrinkle reduction. No commercial nanoemulsion Syn-Ake product widely available as of 2026. DIY nanoemulsion formulation requires specialized equipment and surfactant expertise.
Standard 4% concentration applied immediately post-needling; theoretically higher dermal delivery efficiency via mechanically disrupted barrier, but no published bioavailability data
Community-derived practice: use 0.25–0.5mm dermaroller or microneedle pen on clean skin, then apply Syn-Ake serum while skin remains permeable. Do not exceed 0.5mm depth in delicate periorbital area. Allow 24 hours before layering other actives post-needling. Microneedling alone improves wrinkle appearance through mechanical stimulation: confounds Syn-Ake-specific benefit assessment.
Pre + postsynaptic dual neuromuscular inhibition. SNAP-8 inhibits SNARE complex assembly (presynaptic); Syn-Ake blocks postsynaptic mnAChR epsilon-subunit. Complementary targets at different steps in the acetylcholine contraction cascade.
4% Syn-Ake + 10% SNAP-8 in HA base serum, BID
Collagen-stimulating mechanism (TGF-β pathway) complements Syn-Ake's neuromuscular relaxation. Addresses structural collagen loss while Syn-Ake targets dynamic muscle-driven wrinkle depth.
Combined in same serum or layered AM routine; both 2x daily
Collagen/elastin ECM remodeling at a deeper structural level. GHK-Cu works on matrix architecture; Syn-Ake on surface neuromuscular relaxation. Common pairing in premium multi-peptide serums.
Syn-Ake AM; GHK-Cu PM (or combined in same serum formulation)
Fellow neuromuscular inhibitor via SNARE complex presynaptic pathway. Triple combination with Syn-Ake + Argireline + SNAP-8 covers postsynaptic receptor blockade plus two presynaptic SNARE inhibition points. Mechanistically additive.
All three at 4–10% each in multi-peptide serum; apply BID
Both work through neuromuscular blockade at the same facial muscles. Additive inhibition is theoretically possible. Clinical significance for topical Syn-Ake is likely minimal given <1% systemic absorption, but applying Syn-Ake over fresh injection sites risks unpredictable absorption through disrupted skin barrier. Consult injector before combining.
Compromised skin barrier post-peel alters Syn-Ake absorption unpredictably and may cause excessive irritation. Wait 48–72 hours after peel treatment before resuming application.
Compromised barrier dramatically increases transdermal penetration beyond intended superficial local action. Avoid active dermatitis, eczema flares, open wounds, or sunburned skin at application sites.
Pricing updated 2026-04-09
The most important safety context for Syn-Ake is the gap between what's been studied and what's on the market. No long-term safety study beyond 12 weeks exists for this ingredient as a standalone compound. The total published human evidence comes from roughly 80 subjects across two studies, one of which (Trookman 2009)[1] tested a multi-ingredient formula. That said, the adverse event profile across all available data is clean. Clinical studies at 4% concentration report no significant adverse events. The EWG Skin Deep database rates dipeptide diaminobutyroyl benzylamide diacetate as low risk across all toxicity categories: cancer, allergies, immunotoxicity, developmental and reproductive toxicity. Gok and colleagues [2] confirmed a favorable cytotoxicity and genotoxicity profile in vitro. Rare cases of mild, temporary skin irritation have been reported. Slight redness, tingling, or burning sensation at the application site can occur, particularly in people with sensitive skin or a compromised skin barrier. Allergic contact dermatitis is theoretically possible but has not surfaced at clinically meaningful rates. Systemic side effects are not expected. Syn-Ake acts locally within the upper skin layers. At less than 1% systemic absorption, the peptide doesn't reach meaningful plasma concentrations. No published data reports systemic Cmax, AUC, or elimination half-life. For people receiving botulinum toxin injections: both compounds target neuromuscular transmission in the same facial muscles. The clinical overlap is likely minimal given topical Syn-Ake's low systemic absorption. Still, inform your injector. Applying the peptide over freshly injected sites also risks unpredictable absorption through a disrupted barrier. Contraindications: myasthenia gravis or other neuromuscular junction disorders (theoretical risk of worsening muscle weakness). Pregnancy and breastfeeding (zero safety data in these populations). Children under 18 (no data). Active skin infections, open wounds, or severe dermatitis at intended application sites. Stop use and consult a dermatologist if persistent redness, contact dermatitis, or unusual skin reactions develop that don't resolve with dose reduction.
Verify Syn-Ake dosing and safety with a second opinion
Syn-Ake (SYN®-AKE) is a proprietary ingredient trademarked by DSM-Firmenich (formerly Pentapharm Ltd), a regulated cosmetic ingredient supplier operating under ISO 22716 GMP. The active (CAS 823202-99-9) is a well-characterized synthetic tripeptide. Commercial finished products from established brands undergo standard cosmetic GMP manufacturing. Raw ingredient available from US research peptide vendors (Cenexal Labs, Peptide.shop). Primary quality variable: actual % concentration: products listing "Syn-Ake" without a declared % may deliver sub-therapeutic doses. EWG Skin Deep rates this ingredient low risk across all toxicity categories.
| Test | When | Target |
|---|---|---|
| Baseline + 4-week photography (expression lines) | Week 0 and Week 4 | Visible reduction in expression line depth or roughness in consistent lighting conditions |
| Skin tolerance self-assessment | Days 3, 7, and 14 of initial use | — |
Objective before/after comparison to detect responder status early. Expression wrinkles are highly subject to lighting and facial position bias without standardized photography.
Contact dermatitis or irritant reaction identification. Most reactions present within the first 2 weeks. Allows switching to every-other-day protocol or isolating the vehicle ingredient as the sensitizer.
Subtle smoothing may be noticed immediately after application due to serum vehicle hydration. In vitro data shows 36% muscle contraction reduction within 1 minute and 82% within 2 hours, though topical onset in vivo is slower due to skin penetration time.
Peptide begins accumulating in the upper skin layers with twice-daily application. Some users report a softening of fine surface expression lines. Full neuromuscular effects are building as steady-state skin concentrations are approached.
Measurable wrinkle reduction becomes apparent. The manufacturer 28-day study reported up to 52% improvement in forehead wrinkle depth at this timepoint. Expression lines around the eyes and mouth begin to visibly soften.
Continued improvement in wrinkle depth and skin smoothness. Clinical studies show sustained significant results (p <= 0.0003) through month 3. Deeper expression lines show gradual improvement as sustained muscle relaxation allows the skin to recover from chronic mechanical creasing.
Effects are not permanent. Because Syn-Ake works through reversible receptor binding, muscle contraction returns to normal within 1-2 weeks after discontinuation. Wrinkle depth gradually returns toward baseline as facial muscles resume habitual expression patterns.
Minutes to hours after your first application: don't expect visible wrinkle change. Any immediate smoothing you notice comes from the serum vehicle (usually hyaluronic acid), not the peptide itself. In lab conditions, cultured muscle cells show 36% contraction reduction at one minute and 82% at two hours, but topical delivery through intact skin is slower. Weeks 1 to 2: the peptide accumulates in your upper skin layers with twice-daily application. Its molecular weight (495.58 Da) allows passive diffusion through the stratum corneum. Some users report a subtle softening of fine lines, though this is hard to separate from vehicle hydration at this stage. Weeks 2 to 4: this is where measurable change starts. The manufacturer's 28-day endpoint found up to 52% wrinkle depth reduction in 45 subjects using 4% cream. Community consensus calls this the "you can tell it's doing something" window. If you're a responder, forehead lines and crow's feet start visibly softening. Non-responders see minimal change. Weeks 4 to 12: improvement continues and plateaus around week 6 to 8 for most users. Trookman 2009 (multi-ingredient formulation)[1] confirmed statistically significant wrinkle reduction at every 4-week interval through month 3 (p less than 0.0003). Deeper expression lines improve gradually as sustained muscle relaxation reduces chronic mechanical creasing. Many users shift to once-daily maintenance at this stage. After stopping: effects are not permanent. Syn-Ake binds the acetylcholine receptor reversibly, so muscle contraction returns to normal within one to two weeks. Wrinkle depth returns toward your pre-treatment baseline as habitual expression patterns resume. No rebound worsening has been reported. You can restart the protocol at any point without loss of efficacy.
In vitro: 36% muscle contraction reduction within 1 minute, 82% within 2 hours at 0.025% (cultured muscle cells). Topical in vivo onset is slower due to skin penetration kinetics. Peptide begins accumulating in the stratum corneum.
Some immediate plumping or smoothing sensation attributable to HA serum vehicle hydration, not the peptide. No visible wrinkle reduction expected on first application.
Peptide accumulates toward steady-state concentration in upper skin layers with BID application. Low MW (495.58 Da) enables passive transcorneal diffusion. No measurable clinical wrinkle change at this stage.
Subtle softening of fine surface lines occasionally reported; primarily attributed to vehicle hydration and expectation effects. Distinct wrinkle improvement not yet expected.
Manufacturer's primary endpoint: up to 52% wrinkle depth reduction at day 28 in 45 subjects applying 4% forehead cream. Best available human data for single-compound assessment (manufacturer-funded, not peer-reviewed).
Visible softening of forehead lines and crow's feet in responders. Community commonly identifies this as the "you can tell it's doing something" timepoint. Non-responders see minimal change.
Trookman 2009 (multi-ingredient, confounded): statistically significant wrinkle reduction at all 4-week intervals through month 3 (p≤0.0003). Deeper expression lines show gradual improvement as sustained muscle relaxation reduces chronic mechanical creasing of overlying skin.
Continued improvement that plateaus after week 6–8. Many users adopt maintenance frequency (once daily PM). Skin texture improvement reported beyond wrinkle depth reduction alone.
Reversible competitive receptor binding: muscle contraction returns to normal as Syn-Ake dissociates from mnAChR epsilon subunit. Wrinkle depth returns toward pre-treatment baseline as habitual expression patterns resume. No permanent structural benefit documented.
Consistent with science: lines reappear within 1–2 weeks of stopping. No rebound worsening. Users can restart protocol without loss of efficacy.
Source: No systemic pharmacokinetic data available. Syn-Ake is a topical cosmeceutical peptide with a molecular weight of 495.58 Da that acts locally within the skin. Its small size enables stratum corneum penetration but no published studies report systemic Cmax, AUC, or elimination half-life. The peptide exerts its effects through local receptor binding in the upper dermal layers without significant systemic absorption.
Loading the interactive decay curve.
Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate, Tripeptide-3) is not FDA-approved for any medical indication. It is classified as a cosmeceutical research ingredient. No NDA, BLA, or 510(k) submission exists for this compound. The ingredient is commercially available in finished skincare products sold over the counter as cosmetics, not as drugs or medical devices. The Cosmetic Ingredient Review panel has not flagged safety concerns. It is listed on the EU CosIng database as an approved cosmetic ingredient. Raw peptide powder (CAS 823202-99-9) is available from US research suppliers including Cenexal Labs and Peptide.shop. DSM-Firmenich holds the SYN-AKE trademark for the branded ingredient. Syn-Ake does not appear on the WADA prohibited substances list as of 2026 and is not relevant for athletic drug testing. This content is for informational and research purposes only. It does not constitute medical advice, diagnosis, or treatment. Consult a qualified dermatologist or healthcare provider before beginning any new skincare regimen, particularly if you have a neuromuscular disorder, are pregnant or breastfeeding, or are receiving botulinum toxin injections.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
