Side-by-side · Research reference
AHK-CuvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-MechanisticHUMAN-REVIEWED14/43 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
AHK-Cu
Tripeptide-Copper Complex · Cosmetic
Topical · Scalp / Skin
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
AHK-Cu
PE 22-28
Primary target
Dermal papilla cells (DPCs) — specialized fibroblasts in hair follicle morphogenesisPyo 2007
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
AHK-Cu → DPC proliferation → VEGF elevation, TGF-β1 suppression → Angiogenesis, follicle elongationPyo 2007
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Stimulates hair follicle elongation ex vivo, reduces dermal papilla cell apoptosis, elevates Bcl-2/Bax ratio, reduces cleaved caspase-3 and PARPPyo 2007
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
—
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Synthetic tripeptide with Cu²⁺ chelation — alanine substitution variant of GHK-Cu
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
AHK-Cu
PE 22-28
Effective concentration (in vitro)
10⁻¹² – 10⁻⁹ MPyo 2007
Stimulated human hair follicle elongation ex vivo and DPC proliferation in vitro.
—
Topical formulation
0.001–0.01% (estimated cosmetic range)
No standardized human protocol published — extrapolated from in vitro data.
—
Frequency
Once or twice daily (topical application)
Once daily
Sustained antidepressant effect over 7+ days.
Route
Topical — scalp or dermal application
—
Evidence basis
Ex vivo hair follicle / in vitro DPC studiesPyo 2007
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Duration
Not established — cosmetic protocols typically 8–12 weeks
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
04Side Effects & Safety
Parameter
AHK-Cu
PE 22-28
Local irritation
Mild erythema, pruritus at application site (copper peptide class effect)
—
Copper sensitivity
Rare hypersensitivity reaction in copper-sensitive individuals
—
Systemic absorption
Minimal via topical route — systemic copper toxicity unlikely at cosmetic doses
—
Data limitations
No published human safety trials — cosmetic use presumed safe per class precedent (GHK-Cu)
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
AHK-Cu
- ·Known copper allergy or Wilson's disease
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
AHK-Cu
- ·Broken or inflamed skin (increased absorption risk)
- ·Concurrent use of other copper-containing formulations
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
AHK-Cu
PE 22-28
1. Topical application
Apply to clean, dry scalp or target dermal area. Typical cosmetic formulations: 0.001–0.01% AHK-Cu in serum or cream base.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Frequency
Once or twice daily. Evening application preferred for overnight contact time.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Scalp preparation
For hair growth: apply directly to scalp, massage gently. No need to rinse. Allow absorption for minimum 2–4 hours.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Room temperature, protected from light. Copper complexes may degrade in UV exposure.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Duration
Minimum 8–12 weeks to assess efficacy in hair growth applications, per typical cosmetic peptide protocols.
—
06Stack Synergy
AHK-Cu
+ GHK-Cu
ModerateBoth tripeptide-copper complexes share overlapping angiogenic and wound-healing mechanisms (VEGF elevation, TGF-β modulation, fibroblast proliferation). AHK-Cu's alanine substitution may offer distinct receptor affinity or pharmacokinetics. Co-formulation could provide complementary dermal signaling, though no direct synergy studies exist. Often used interchangeably or in alternating protocols.
- AHK-Cu
- 0.001–0.01% topical · AM
- GHK-Cu
- 0.001–0.01% topical · PM
- Frequency
- Daily alternation or combined formulation
- Primary benefit
- Comprehensive dermal regeneration, angiogenesis, hair follicle support
PE 22-28
— no documented stacks