Side-by-side · Research reference
PE 22-28vsSemax
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
BHuman-MechanisticAUTO-DRAFTED12/39 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
Semax
Cognitive enhancer · Russian Pharma
Intranasal · 2–3×/day during cognitive demand
01Mechanism of Action
Parameter
PE 22-28
Semax
Primary target
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
BDNF / NGF expression + monoamine modulationKaplan 2017
Pathway
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
↑ BDNF + NGF synthesis + 5-HT modulation → neuroplasticity + anxiolysis + cognitive enhancementKaplan 2017
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 2017Cong 2023Wu 2021
Improved memory + attention; reduced anxiety; neuroprotection in ischemiaKaplan 2017
Feedback intact?
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
—
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 2017Mazella 2018
Synthetic 7-AA peptide derived from ACTH(4-7) with C-terminal Pro-Gly-Pro stabilising tailKaplan 2017
Antibody development
Not reported in animal studies
—
02Dosage Protocols
Parameter
PE 22-28
Semax
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.
2–3× per day during cognitive demand
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.
—
Evidence basis
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Human-mechanistic + Russian clinicalKaplan 2017
Lower / starter dose
—
100 mcg / dose
Duration
—
10–14 day cycles, repeated PRN
Reconstitution
—
Pre-formulated nasal spray (commercial); research vial: bacteriostatic water
Timing
—
Morning + early afternoon
Half-life
—
Short plasma; CNS effect lasts ~3–6 hr
04Side Effects & Safety
Parameter
PE 22-28
Semax
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
Limited Western RCT data
Nasal irritation
—
Mild burning or congestion (transient)
Sleep disruption
—
Late-day dosing may interfere with sleep
Headache
—
Uncommon, transient
Pregnancy / OB
—
Avoid
Absolute Contraindications
PE 22-28
- ·Human use — no clinical safety data available
Semax
- ·Pregnancy / breastfeeding
Relative Contraindications
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
Semax
- ·Active psychiatric instability
- ·Concurrent strong stimulants
05Administration Protocol
Parameter
PE 22-28
Semax
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.
Pre-formulated nasal spray (commercial) or research vial reconstituted with bacteriostatic water.
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
Intranasal — 2–3 sprays per nostril per dose. Tilt head slightly back.
3. BBB penetration
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
Morning + early afternoon. Avoid evening (sleep disruption).
4. Human formulation
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
Refrigerate after reconstitution; light-protected.
5. Caveat
—
Cycle on/off to avoid neurochemical adaptation.
06Stack Synergy
PE 22-28
— no documented stacks
Semax
+ Selank
ModerateSemax (cognitive enhancer, BDNF/NGF) and Selank (anxiolytic + immune) form the canonical Russian "neuro stack" — both intranasal peptide bioregulators with complementary axes. Semax for cognitive demand; Selank for stress mitigation.
- Semax
- 200–600 mcg intranasal · morning + afternoon
- Selank
- 150–300 mcg intranasal · midday + early evening
- Primary benefit
- Cognitive enhancement + stress mitigation