Side-by-side · Research reference
CortagenvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-MechanisticHUMAN-REVIEWED11/35 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
Cortagen
Bioregulatory Tetrapeptide · Khavinson-School
Injectable · Animal models
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
Cortagen
PE 22-28
Primary target
Cerebral cortex tissue — molecular targets under investigation
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
Antioxidant pathway modulation — suppression of LPO cascade, reduction of protein oxidative modificationKozina 2007
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Decreased lipid peroxidation products, reduced oxidative protein damage, altered gene expression in cardiac tissueKozina 2007Anisimov 2004
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 tetrapeptide derived from amino acid analysis of natural brain cortex peptide preparation CortexinAnisimov 2004
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
Cortagen
PE 22-28
Animal model dose (rat)
Injection protocol (dose not specified in abstracts)
Multiple injections over study period.
—
Avian model dose (chicken)
40-day injection courseKuznik 2008
Compared to epithalon in hypophysectomized and aged birds.
—
Human peripheral nerve study
Therapeutic course (protocol details not provided)
Posttraumatic recovery context — reference cited but not detailed.
—
Evidence basis
Animal mechanistic studies
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Route
Injectable (inferred from animal protocols)
—
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.
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
Cortagen
PE 22-28
Antioxidant suppression
Suppression of antioxidant activity noted alongside LPO reductionKozina 2007
Mechanism unclear — possible homeostatic adaptation.
—
Immune/hemostasis effects
No effect on immunity or hemostasis parameters in avian hypophysectomy model (unlike epithalon)Kuznik 2008
Epithalon reversed deficits; cortagen did not.
—
Human safety data
No adverse events reported in peripheral nerve recovery context
Limited detail in available abstracts.
—
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
Cortagen
—PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
Cortagen
—PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
Cortagen
PE 22-28
1. Preparation
Reconstitute lyophilised peptide with bacteriostatic water per supplier protocol. Exact volumes depend on concentration supplied.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Injection site
Subcutaneous injection typical for bioregulatory peptides — abdomen or thigh. Rotate sites.
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
Animal protocols used repeated dosing over weeks. Human timing not established — evening administration common in Khavinson tradition.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Lyophilised: refrigerate or freeze per supplier. Reconstituted: refrigerate 2–8 °C, use within guideline window.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.