Side-by-side · Research reference

PE 22-28vsVilon

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED16/47 cited

BAnimal-StrongHUMAN-REVIEWED13/49 cited

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

Vilon

Khavinson Bioregulator · Dipeptide

2 AADipeptide

T-helperStimulatesLinkova 2011

MouseModel basisKhavinson 2002

Literature lacks standardised clinical route

01Mechanism of Action

Parameter

PE 22-28

Vilon

Primary target

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Immune cell differentiation pathways, chromatin modification

Pathway

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

Vilon → Thymocyte sphingomyelinase activation → T-helper & cytotoxic T-cell differentiation; epigenetic suppression of aging markers (CCL11, HMGB1)

Downstream effect

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

Enhanced T-cell differentiation (CD4+, CD8+, B-cells), thymocyte proliferation, modulated IL-1β comitogenic activity, proposed chromatin decondensation in aged lymphocytesLinkova 2011 Khavinson 2002 Lezhava 2023

Feedback intact?

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Unknown — no HPA/HPG axis data

Origin

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 2017 Mazella 2018

Synthetic dipeptide derived from Khavinson thymic peptide extraction studies (Thymalin fraction)Morozov 1997

Antibody development

Not reported in animal studies

—

02Dosage Protocols

Parameter

PE 22-28

Vilon

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.

—

Frequency

Once daily

Sustained antidepressant effect over 7+ days.

Unknown — literature does not specify chronic administration protocols

Onset (animal)

Within hours (acute); full effect 4–7 days

—

Duration (animal)

7–28 days testedQi 2018 Pietri 2019

—

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.

—

Evidence basis

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

Mouse / in vitro only

Standard dose

—

No clinical standard — literature lacks human dosing

Russian practice: often combined with other Khavinson peptides; no FDA/EMA trials.

Animal model dose

—

In vitro: 0.01–10 μg/mL culture medium (mouse thymocytes)

Not translatable to human mg/kg without pharmacokinetic data.

Duration

—

Not characterised in humans

Route

—

Likely SQ or oral (Khavinson school uses both); no published ROA validation

Half-life

—

Not published — dipeptides typically <10 min plasma t½

04Side Effects & Safety

Parameter

PE 22-28

Vilon

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

—

Human safety data

—

Absent from PubMed-indexed literature

Theoretical risk

—

Immune hyperactivation in autoimmune-prone individuals (T-cell differentiation enhancement)

Antibody formation

—

Not reported; dipeptides generally low immunogenicity

Animal models

—

No adverse effects noted in mouse thymocyte or pineal lymphoid cultures

Absolute Contraindications

PE 22-28

·Human use — no clinical safety data available

Vilon

·Active autoimmune disease (theoretical — no clinical data)

Relative Contraindications

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

Vilon

·Pregnancy / lactation (no safety data)
·Acute infection with cytokine storm risk (immune modulation unknown)

05Administration Protocol

Parameter

PE 22-28

Vilon

1. Animal protocol (IP)

Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.

No clinical protocols exist in Western peer-reviewed literature. Russian gerontological practice may use 1–10 mg ranges, but dosing is empirical.

2. Stability

Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017

Subcutaneous injection (common for Khavinson peptides) or oral (some bioregulators reportedly active orally due to small size). No validated ROA.

3. BBB penetration

Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.

Unknown — no circadian or meal-timing data. Khavinson school often recommends morning administration.

4. Human formulation

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

Likely lyophilised powder, refrigerated. Reconstitution protocols not published.

06Stack Synergy

PE 22-28

— no documented stacks

Vilon

+ Epitalon

Moderate

View Epitalon →

Both are Khavinson bioregulators targeting aging pathways. Epitalon (Ala-Glu-Asp-Gly) acts on telomerase and pineal function; Vilon on immune differentiation and chromatin decondensation. Combined in Russian gerontological protocols for multi-system aging intervention. Lezhava et al. (2023) tested both on aged lymphocyte chromatin, showing distinct epigenetic effects. Complementary, not synergistic in strict pharmacological sense.

Vilon: Empirical — no standard
Epitalon: Empirical — often 10 mg cycles
Frequency: Sequential or concurrent (literature ambiguous)
Primary benefit: Multi-system aging modulation (immune + pineal/circadian)

+ Thymalin

Weak

View Thymalin →

Thymalin is the parent polypeptide complex from which Vilon was isolated. Both target immune differentiation, but Thymalin is a complex mixture (multiple peptides), whereas Vilon is a purified dipeptide. Morozov & Khavinson (1997) described Vilon as a synthetic successor designed to replicate Thymalin's immunomodulatory effects with greater specificity. Redundant in practice; no published combination studies.

Vilon: No standard
Thymalin: 10–100 mg IM (polypeptide complex)
Primary benefit: Redundant — both target T-cell differentiation

Morozov 1997 Khavinson 2020