Preclinical2017
Shortened spadin analogs (including PE 22-28) displayed better TREK-1 inhibition and in-vivo stability than spadin, with antidepressant-like activity in mouse behavioral tests.
TREK-1 channel inhibition
anecdotalCognitive
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PE-22-28
BDNF fragment peptide for cognitive enhancement and neuroprotection
Overview
PE-22-28 is a synthetic peptide fragment of Brain-Derived Neurotrophic Factor (BDNF) that may promote neurogenesis, enhance synaptic plasticity, and protect neurons. Research suggests potential for improving memory, learning, and cognitive function. May benefit neurodegenerative diseases and age-related cognitive decline. Represents a novel approach to cognitive enhancement through neurotrophin signaling.
Last reviewed: 2026-08-18
Identity & Aliases
Also known as
PE 22-28PE22-28spadin analogTREK-1 channel inhibitor peptide
Full composition (formula, molecular weight, sequence) in Quick Facts →
Research Areas
Antidepressant researchTREK-1 (KCNK2) potassium channel modulationNeuroplasticityPsychiatric disorders
Available Evidence
Animal
In mice, shortened spadin analogs including PE 22-28 showed better TREK-1 channel inhibition and in-vivo stability than the parent peptide spadin, and produced antidepressant-like activity in behavioral tests (for example, the forced swim test).
In Vitro
Electrophysiological assays in cell systems show PE 22-28 inhibits TREK-1 background potassium channels; TREK-1 is of interest in depression because its genetic deletion produces antidepressant-like phenotypes.
Uncertain
Any antidepressant efficacy in humans is entirely speculative; no human clinical trials exist, and the 'sexual wellness' categorization seen in some retail listings reflects marketing, not published research.
Key Studies & Findings
Benefits & Effects
Side Effects & Safety
Limitations & Open Questions
Evidence is exclusively preclinical: no human studies, no pharmacokinetic or safety data in humans; claims of mood or libido benefits are speculative.
Pharmacology
PE 22-28 is a shortened analog of spadin, a peptide ligand related to the sortilin/neurotensin receptor pathway; it blocks TREK-1 (KCNK2) two-pore-domain potassium channels. Route and dosing for research use are not standardized in published literature.
Reported Research Dosing
Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.
dosage not established
Route: SC
Half-life: 23 hours (vs 7h for spadin)
Research Protocols
Preclinical Antidepressant Studies (Mouse)
- Dose
- 3-4 mcg/kg
- Frequency
- Once daily
- Route
- Intraperitoneal (IP)
Preclinical Oral Studies (Mouse)
- Dose
- 1 mg/kg
- Frequency
- Once daily
- Route
- Oral gavage
Research Protocol (Human Equivalent - Theoretical)
- Dose
- 50-100 mcg
- Frequency
- Once daily
- Route
- Subcutaneous
Research Protocol (Conservative)
- Dose
- 100-200 mcg
- Frequency
- Once daily
- Route
- Subcutaneous
Research protocols are for educational purposes only. Always consult qualified medical professionals.
Frequently Asked Questions
Has PE-22-28 been tested in humans?
No. All published data are from in-vitro and mouse studies; no human clinical trials have been conducted.
Why is TREK-1 a target of interest?
TREK-1 is a background potassium channel implicated in mood regulation; inhibiting it produces antidepressant-like effects in animal models.
Research Citations
1
Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M (2017)
2
Antenatal risk stratification for preeclampsia with sFlt-1/PlGF ratio: Which is the best time to test?
Kumar M, Balyan K, Debnath E, Himtsoe B, Sapna S, Kumar A (2023)
3
Morphology of pollen in Ferula genus (Apiaceae).
Baser B, Sagıroglu M, Dogan G, Duman H (2021)
4
The cardio-ankle vascular index as a predictor of adverse pregnancy outcomes.
Rueangjaroen P, Luewan S, Phrommintikul A, Leemasawat K, Tongsong T (2021)
5
Materno-fetal outcome with PlGF above or below cutoff during second half of pregnancy in high-risk women.
Balyan K, Humtso BY, Meena B, Sapna S, Rana A, Kumar M (2024)
+ 20 more citations
Related Resources
Quick Facts
Formula
C96H142N26O22
Molecular Weight
750.0
Sequence
MRRGERRDAGGPRPESPVPAGRASLEEPPDGPSAGQATGPGEGRRSTESEVYDDGTNTFFWRAHTLTVLFILTCTLGYVTLLEETPQDTAYNTKRGIVASILVFLCFGVTQAKDGPFSRPHPAYWRFWLCVSVVYELFLIFILFQTVQDGRQFLKYVDPKLGVPLPERDYGGNCLIYDPDNETDPFHNIWDKLDGFVPAHFLGWYLKTLMIRDWWMCMIISVMFEFLEYSLEHQLPNFSECWWDHWIMDVLVCNGLGIYCGMKTLEWLSLKTYKWQGLWNIPTYKGKMKRIAFQFTPYSWVRFEWKPASSLRRWLAVCGIILVFLLAELNTFYLKFVLWMPPEHYLVLLRLVFFVNVGGVAMREIYDFMDDPKPHKKLGPQAWLVAAITATELLIVVKYDPHTLTLSLPFYISQCWTLGSVLALTWTVWRFFLRDITLRYKETRWQKWQNKDDQGSTVGNGDQHPLGLDEDLLGPGVAEGEGAPTPN
Mechanism
Cognitive enhancement peptide derived from TREK-1 channel modulation
Safety Information
Research compound only. Shortened spadin analog. Limited human safety data available.
Citations
251.Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.
Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M (2017)
2.Antenatal risk stratification for preeclampsia with sFlt-1/PlGF ratio: Which is the best time to test?
Kumar M, Balyan K, Debnath E, Himtsoe B, Sapna S, Kumar A (2023)
3.Morphology of pollen in Ferula genus (Apiaceae).
Baser B, Sagıroglu M, Dogan G, Duman H (2021)
4.The cardio-ankle vascular index as a predictor of adverse pregnancy outcomes.
Rueangjaroen P, Luewan S, Phrommintikul A, Leemasawat K, Tongsong T (2021)
5.Materno-fetal outcome with PlGF above or below cutoff during second half of pregnancy in high-risk women.
Balyan K, Humtso BY, Meena B, Sapna S, Rana A, Kumar M (2024)
+ 20 more citations