Side-by-side · Research reference
PE 22-28vsPinealon
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-DRAFTED12/36 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
Pinealon
Pineal-derived · Neuroprotective
SQ or IM · Daily for 10 days · 1-2×/year
01Mechanism of Action
Parameter
PE 22-28
Pinealon
Primary target
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Antioxidant defense + neuronal gene expression (proposed)Khavinson 2014
Pathway
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Modulation of antioxidant enzymes (SOD, catalase) + neurotrophic factor expressionKhavinson 2014
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
Reduced oxidative stress in neurons; improved cognitive function in age-related declineKhavinson 2014
Feedback intact?
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
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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 4-AA peptide derived from pineal gland extractKhavinson 2014
Antibody development
Not reported in animal studies
—
02Dosage Protocols
Parameter
PE 22-28
Pinealon
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.
Once daily during cycle
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
Russian clinical trials + in vitroKhavinson 2014
Lower / starter dose
—
2.5 mg / day
Duration
—
10-day cycles, 1–2× per year
Reconstitution
—
Bacteriostatic water
Timing
—
No specific time
Half-life
—
Hours
04Side Effects & Safety
Parameter
PE 22-28
Pinealon
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 data
Injection site reaction
—
Mild irritation
Pregnancy / OB
—
Avoid
Absolute Contraindications
PE 22-28
- ·Human use — no clinical safety data available
Pinealon
- ·Pregnancy / breastfeeding
Relative Contraindications
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
Pinealon
- ·Active malignancy (theoretical via gene expression modulation)
05Administration Protocol
Parameter
PE 22-28
Pinealon
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.
Add 1–2 mL bacteriostatic water to 10 mg vial.
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
SQ — abdomen preferred.
3. BBB penetration
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
Daily during cycle, any time.
4. Human formulation
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
Lyophilised: room temp. Reconstituted: refrigerate ≤30 days.
5. Needle
—
29–31G, 4–8 mm insulin syringe.
06Stack Synergy
PE 22-28
— no documented stacks
Pinealon
+ Epitalon
ModeratePinealon (neuroprotection) + Epitalon (telomerase activation) form the canonical Khavinson "longevity stack" — both pineal-derived bioregulators with complementary axes. Pinealon supports neuronal antioxidant defense; Epitalon supports telomere maintenance. Anecdotally cycled together 1–2× per year.
- Pinealon
- 5–10 mg SQ · daily × 10 days
- Epitalon
- 5–10 mg SQ · daily × 10 days (overlap or alternate)
- Primary benefit
- Neuroprotection + telomere preservation