Side-by-side · Research reference
PancragenvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED23/39 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Pancragen
PE 22-28
Primary target
Pancreatic acinar and islet cell differentiation pathwaysKhavinson 2013
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
Transcription factor activation → Pdx1/Pax6/Pax4/Ptf1a/Foxa2/NKx2.2 upregulation → Cell differentiationKhavinson 2013
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Enhanced pancreatic beta-cell function, normalized insulin/C-peptide dynamics, improved glucose clearanceGoncharova 2014
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?
Yes — preserves physiological glucose-insulin response
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Synthetic tetrapeptide derived from pancreatic tissue extracts (Khavinson bioregulator methodology)
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
Pancragen
PE 22-28
Primate dose (rhesus macaque)
50 μg / animal / dayGoncharova 2014
20–25-year-old females, 10-day IM protocol.
—
Effective concentration (in vitro)
0.05 ng/mLZakutskiĭ 2006
Organotypic tissue culture, both young and aged rat explants.
—
Frequency
Once daily for 10 daysGoncharova 2014
Once daily
Sustained antidepressant effect over 7+ days.
Evidence basis
Non-human primate RCT, in vitro cell cultureGoncharova 2015Khavinson 2013
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Diabetes model
STZ-induced diabetes (rat)
Evaluated via metabolic markers characterizing apoptosis.
—
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
Pancragen
PE 22-28
Reported adverse events
None documented in primate studies
—
Human safety data
No published human trials; clinical use limited to Russian gerontology protocols
—
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
Pancragen
—PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Pancragen
- ·Active pancreatic malignancy (proliferation marker upregulation)
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Pancragen
PE 22-28
1. Reconstitution
Lyophilised tetrapeptide reconstituted in sterile saline or water per manufacturer protocol. Concentration not specified in literature.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Route
Intramuscular injection. Primate studies used daily IM dosing for 10 consecutive days.Goncharova 2015
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Timing
No specific timing constraints documented. Administered once daily in primate protocols.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Cycle structure
10-day treatment course. Restorative effects on pancreatic function persist for at least 3 weeks post-discontinuation.Goncharova 2014
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.