Pentapeptide-18 (CAS 64963-01-5) is supplied by TCS NEXUS S.L. (Valencia, Spain) for European cosmetic formulators, brand R&D teams and B2B buyers reviewing GABAergic pathway modulation, expression-line serum and neuromuscular-relaxation raw material applications. A freely water-soluble enkephalin-mimetic pentapeptide, it dissolves directly in aqueous concentrates without co-solvents at pH 4.5–7.0, with cool-down addition below 40°C recommended in standard serum and leave-on manufacturing protocols.
> Technical Specifications
| Product Name | Pentapeptide-18 (Leuphasyl) |
|---|---|
| Molecular Structure |  |
| CAS Number | 64963-01-5 |
| Alias / Common Name | Pentapeptide-18; Leuphasyl; [D-Ala²]leucine-enkephalin analog |
| Molecular Formula | C29H39N5O7 |
| Molecular Weight | 569.6 g/mol |
| INCI Name | Pentapeptide-18 |
| Peptide Sequence | Tyr-D-Ala-Gly-Phe-Leu — leucine-enkephalin biomimetic (GABAergic modulation) |
| Purity / Assay | ≥98% (HPLC); confirm by batch COA |
| Appearance | White to off-white powder |
| Solubility / Handling | Freely water-soluble; dissolve in deionised water or aqueous phase before incorporation; no co-solvent required |
| pH Stability | Optimal stability at pH 4.5–7.0; confirm in target base after all actives incorporated |
| Storage | Store sealed in cool, dry conditions protected from direct light and moisture; follow batch COA and SDS |
> Mechanism & Positioning
Pentapeptide-18 (CAS 64963-01-5) is a synthetic enkephalin-mimetic pentapeptide based on the leucine-enkephalin sequence, designed to interact with presynaptic enkephalin receptors (δ-opioid receptor subtype) at the neuromuscular junction and modulate GABAergic signalling pathways. Published Pentapeptide-18 literature discusses that the peptide acts as an enkephalin receptor agonist, reducing presynaptic calcium ion (Ca²⁺) influx through voltage-gated calcium channels — a key step in the signal cascade linking nerve depolarisation to acetylcholine vesicle release. Cell-based neuromuscular studies document that reduced presynaptic Ca²⁺ influx attenuates acetylcholine release from presynaptic vesicles, decreasing the frequency and amplitude of muscle contraction signals in neuromuscular junction model assays at peptide concentrations evaluated in formulation-relevant ranges. Neuromuscular model data also notes that the GABAergic mechanism of Pentapeptide-18 operates independently of the SNARE complex pathway targeted by SNAP-25 biomimetics such as Argireline, enabling non-competing multi-pathway neuromuscular signal attenuation when both are combined.
Based on available in vitro data, Pentapeptide-18 is positioned for expression-line serum, anti-wrinkle concentrate and periorbital formulation concepts where GABAergic presynaptic Ca²⁺ modulation is the primary mechanistic direction. Its pathway independence from the SNARE complex differentiates it from Argireline (Acetyl Hexapeptide-8) (SNARE/SNAP-25 N-terminal biomimetic) and from Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate) (postsynaptic nAChR modulation), enabling three-mechanism neuromuscular positioning across presynaptic SNARE inhibition, GABAergic modulation and postsynaptic nAChR modulation.
> Application Concepts
Expression Line Serum Architecture
Pentapeptide-18 is freely water-soluble and dissolves directly in glycerin–water concentrates, hyaluronic acid solutions and buffered aqueous serum bases at evaluation concentrations of 0.001–0.01% (w/w) without co-solvent or glycol pre-mix. Introduce during the cool-down phase below 40°C; standard serum manufacturing cool-down protocols are fully compatible with this addition requirement. The water-soluble profile allows clean addition to clear aqueous serums, layering serums and pump-format concentrates where aesthetic transparency is a formulation priority. For single-mechanism expression-line positioning, Pentapeptide-18 delivers GABAergic presynaptic Ca²⁺ pathway modulation as a standalone active in lightweight serum bases. Confirm clarity, pH (4.5–7.0) and peptide assay retention via accelerated stability testing at 40°C/75% RH before scale-up.
Multi-Peptide Neuromuscular Relaxation Systems
Pentapeptide-18 (GABAergic / presynaptic Ca²⁺ pathway) builds three-mechanism neuromuscular signal attenuation systems with: Argireline (Acetyl Hexapeptide-8) — SNARE complex / SNAP-25 N-terminal biomimetic, targeting synaptic vesicle docking and membrane fusion presynaptically; Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate) — postsynaptic nicotinic acetylcholine receptor (nAChR) modulation, attenuating the postsynaptic depolarisation signal. All three are freely water-soluble and stable at pH 4.5–7.0; combine them in a single aqueous serum phase without emulsification or co-solvent requirements. Confirm combined peptide assay retention, pH and preservative compatibility in the finished concentrate before committing to scale-up batches.
Periorbital and Forehead Targeted Formulations
The GABAergic presynaptic mechanism makes Pentapeptide-18 particularly suited for periorbital and forehead treatments where expression lines from repeated orbicularis oculi and frontalis muscle contraction are the formulation focus. At 0.001–0.01% (w/w), Pentapeptide-18 integrates into lightweight eye-contour gels, cream-gel eye treatments and hydrogel patches without auxiliary solvents, keeping periorbital formulation systems clean and well-tolerated. Evaluate compatibility with niacinamide (2–5%), caffeine (0.5–2.0%) and hyaluronic acid at pH 5.0–6.5; confirm pH alignment across all actives. For comprehensive periorbital neuromuscular positioning, Pentapeptide-18 (GABAergic) may be evaluated alongside Argireline (SNARE pathway) to address two independent presynaptic mechanisms in a single concentrate. Confirm combined peptide stability and assay retention before scale-up.
> Handling & Formulation Notes
Dissolve Pentapeptide-18 in deionised water or the aqueous phase at ambient temperature; the peptide is freely water-soluble and does not require co-solvent, glycol pre-mix or surfactant dispersion. Introduce the aqueous solution during the cool-down phase at temperatures below 40°C — avoid prolonged exposure above 45°C. Maintain formulation pH within 4.5–7.0 for optimal stability; confirm pH after all actives, acids and buffering agents are incorporated into the finished batch.
Evaluate compatibility with EDTA and other chelating agents at typical cosmetic concentrations. Confirm colour, clarity and peptide assay retention via accelerated stability testing at 40°C/75% RH across the intended shelf-life period before scale-up to production batches.
> Supply & Documentation
Pentapeptide-18 (CAS 64963-01-5) is available from TCS NEXUS S.L. (Valencia, Spain) for B2B cosmetic raw material projects. Standard documentation: COA, TDS, SDS. Sample and bulk quantities are discussed on a per-project basis; contact info@tcspeptides.com to initiate a sourcing review.
TCS NEXUS S.L. supports procurement and formulation teams in Germany, France, Italy, Spain, the United Kingdom, the Netherlands, Belgium, Poland, Sweden and Portugal, as well as international buyers in the United States, Canada, Japan, South Korea, Australia and New Zealand.
> Packaging & Storage
Pentapeptide-18 is supplied in sealed aluminium foil bags or bulk containers. Minimum quantities and packaging configurations are confirmed per order. Store below 25°C in a cool, dry location, away from moisture and direct light. Follow batch COA and SDS for specific storage and handling conditions.
> FAQ
What is Pentapeptide-18 (Leuphasyl)?
Pentapeptide-18 (Leuphasyl, CAS 64963-01-5) is a synthetic enkephalin-mimetic pentapeptide based on the leucine-enkephalin sequence (Tyr-D-Ala-Gly-Phe-Leu), supplied by TCS NEXUS S.L. (Valencia, Spain) as a B2B cosmetic ingredient. It is designed to interact with presynaptic enkephalin receptors (δ-opioid receptor subtype) to modulate GABAergic signalling and attenuate presynaptic calcium influx at the neuromuscular junction, positioning it for expression-line serum and anti-wrinkle concentrate applications.
What is the CAS number for Pentapeptide-18, and what does “Leuphasyl” refer to?
The CAS number for Pentapeptide-18 is 64963-01-5. “Leuphasyl” is a widely used commercial name for the same molecule (INCI: Pentapeptide-18, CAS 64963-01-5). For regulatory documentation and CPNP notification, use the INCI name Pentapeptide-18 consistently; confirm CAS 64963-01-5 against the batch COA when building product files.
How does Pentapeptide-18 work at a molecular level — what is the GABAergic mechanism?
Pentapeptide-18 is an enkephalin-mimetic peptide that acts as an agonist at presynaptic enkephalin receptors (δ-opioid receptor subtype) at the neuromuscular junction. Published Pentapeptide-18 literature discusses that receptor activation reduces presynaptic Ca²⁺ influx through voltage-gated calcium channels — a critical step in the cascade that triggers acetylcholine vesicle release into the synaptic cleft. Cell-based studies document attenuated acetylcholine release and reduced neuromuscular contraction signalling in model assays. The GABAergic Ca²⁺ pathway mechanism is independent of the SNARE complex targeted by Argireline, enabling additive multi-pathway neuromuscular positioning.
How does Pentapeptide-18 differ from Argireline (Acetyl Hexapeptide-8), and how do they complement each other?
Argireline (Acetyl Hexapeptide-8) targets the SNARE complex — specifically competing with native SNAP-25 to interfere with synaptic vesicle docking and membrane fusion. Pentapeptide-18 targets a different presynaptic step: enkephalin receptor agonism to reduce voltage-gated Ca²⁺ influx, which is upstream of vesicle docking. Because the two mechanisms target independent steps in the presynaptic acetylcholine release cascade, combining Argireline and Pentapeptide-18 provides complementary signal attenuation across two non-competing neuromuscular pathways in a single aqueous serum concentrate.
What concentration range should be evaluated for Pentapeptide-18 in expression-line serums?
Formulation literature positions Pentapeptide-18 evaluation at 0.001–0.01% (w/w) in aqueous serum and leave-on systems. The appropriate use level depends on the complete formulation system, active combination, stability protocol and claim direction. TCS NEXUS S.L. confirms evaluation ranges per project scope; contact info@tcspeptides.com with project specification.
What actives combine well with Pentapeptide-18 in multi-peptide neuromuscular systems?
Pentapeptide-18 (GABAergic / presynaptic Ca²⁺) builds three-mechanism neuromuscular systems with: Argireline (Acetyl Hexapeptide-8) — SNARE complex / SNAP-25 N-terminal biomimetic, targeting vesicle docking presynaptically; Syn-Ake (Dipeptide Diaminobutyroyl Benzylamide Diacetate) — postsynaptic nAChR modulation, attenuating the postsynaptic depolarisation response. All three are water-soluble and stable at pH 4.5–7.0; they can be combined in a single aqueous serum phase. For broader age-care positioning, Pentapeptide-18 may also be combined with Matrixyl (Palmitoyl Pentapeptide-4/3) for matrix-synthesis support alongside neuromuscular positioning.
Is Pentapeptide-18 suitable for periorbital and eye-contour formulations?
Pentapeptide-18 is well-suited for periorbital and eye-contour applications: the GABAergic presynaptic mechanism targets expression lines driven by repeated orbicularis oculi and crow’s-feet muscle contraction, and the peptide is freely water-soluble without co-solvents that would complicate eye-area formulation. It integrates into lightweight eye-contour gels, cream-gel treatments and hydrogel patches at cool-down addition below 40°C. Evaluate compatibility with niacinamide and caffeine; confirm pH alignment within 4.5–7.0 across all actives.
How should Pentapeptide-18 (Leuphasyl) be incorporated during manufacturing?
Pentapeptide-18 is freely water-soluble — dissolve it in deionised water or the aqueous phase without a co-solvent, and add it during the cool-down phase below 45°C to avoid heat degradation. Standard aqueous serum and light-emulsion cool-down protocols suit it well; confirm assay retention with accelerated stability testing before scale-up.
What pH range keeps Pentapeptide-18 stable in a finished formula?
Pentapeptide-18 is most stable at pH 4.5–7.0, matching typical serum and light-emulsion targets. Confirm the finished-product pH after all actives and buffering agents are incorporated, and evaluate combined stability when it shares a base with low-pH actives such as ascorbic acid.
What is Leuphasyl’s enkephalin origin, and why the D-Ala² design?
Pentapeptide-18 (Leuphasyl) has the sequence Tyr-D-Ala-Gly-Phe-Leu, a synthetic analogue of the natural opioid peptide leucine-enkephalin. The D-alanine substitution at position 2 replaces the natural residue to resist peptidase breakdown, which is what makes this enkephalin-derived sequence stable enough to use as a freely water-soluble cosmetic raw material.
How should Pentapeptide-18 be stored?
Store Pentapeptide-18 (CAS 64963-01-5) sealed below 25°C in a cool, dry location protected from direct light and moisture. Once opened, reseal the container immediately. Follow specific storage and handling conditions stated in the SDS and batch COA. Confirm shelf life for the specific batch before incorporating into production formulations.
What documentation does TCS NEXUS S.L. provide for Pentapeptide-18?
TCS NEXUS S.L. provides COA (confirming CAS 64963-01-5 and HPLC purity ≥98%), TDS (Technical Data Sheet) and SDS (Safety Data Sheet) for Pentapeptide-18. Additional documentation such as specification sheets and INCI confirmation letters is available on a per-project basis. Contact info@tcspeptides.com to initiate a documentation and sourcing discussion.
What MOQ and sample options are available for Pentapeptide-18?
Sample and bulk quantities for Pentapeptide-18 are confirmed on a per-project basis through TCS NEXUS S.L. Minimum order quantities depend on current stock, packaging configuration and project scope. R&D teams are encouraged to request samples for stability and concentration-range evaluation before bulk planning. Contact info@tcspeptides.com with project specification to begin a sourcing review.
Is Pentapeptide-18 (INCI) compliant with EU Cosmetics Regulation 1223/2009?
Pentapeptide-18 is not listed as a restricted, prohibited or regulated substance under EU Cosmetics Regulation 1223/2009 Annexes II–VI. The finished product manufacturer is responsible for the CPSR and CPNP notification. Use CAS 64963-01-5 and INCI name Pentapeptide-18 consistently in all regulatory documentation; confirm purity and identity against the batch COA.
> Technical Support and Samples
Request COA documents, sample availability, or support for custom synthesis.