PE 22-28
also known as mini-spadin, shortened spadin, spadin fragment
Seven-amino-acid fragment of spadin (PE 12-28), a sortilin-derived peptide that selectively blocks TREK-1 potassium channels. Demonstrates potent antidepressant-like activity in rodent models at sub-nanomolar concentrations (IC50 0.12 nM vs 40-60 nM for full spadin). Shorter sequence confers enhanced in vivo stability, blood-brain barrier penetration, and improved therapeutic window. Pre-clinical only — no human trials reported.
At a glance
IP · SQ · Once Daily (animal models)
Primary target — TREK-1 two-pore-domain potassium channel [djillani-2017][ma-2020].
Pathway — TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity.
Downstream effect — Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulation [djillani-2017][cong-2023][wu-2021].
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-2017][mazella-2018].
Feedback intact — N/A — direct ion channel blockade; not receptor-mediated endocrine axis.
| Parameter | Value |
|---|---|
| Animal dose (antidepressant) | 0.3–3 µg/kg IPEffective in forced swim test, tail suspension test, CUMS models. |
| Animal dose (neuroprotection) | 0.03 µg/kg IP [pietri-2019]Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade. |
| Frequency | Once dailySustained antidepressant effect over 7+ days. |
| Onset (animal) | Within hours (acute); full effect 4–7 days |
| Duration (animal) | 7–28 days tested [qi-2018][pietri-2019] |
| Comparison to fluoxetine | PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7Chronic administration shows superior long-term efficacy. |
| Human equivalent (extrapolated) | Not established — no clinical trialsAllometric scaling from rodent data unavailable. |
| Evidence basis | Multiple rodent RCTs; behavioral + electrophysiology endpoints [djillani-2017][qi-2018][wu-2021] |
Reconstitution
A pure mass-to-volume utility. Enter what you have in the vial; the atlas computes the volume per dose. No prescription information.
- — Human use — no clinical safety data available
- — Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
- 01Animal protocol (IP)
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
- 02Stability
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols. [djillani-2017]
- 03BBB penetration
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
- 04Human formulation
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
Sources
of 47 rendered claims carry a resolvable citation.
- [cong-2023]Cong 2023 — Blocking Two-Pore Domain Potassium Channel TREK-1 Inhibits the Activation of A1-Like Reactive Astrocyte Through the NF-κB Signaling Pathway in a Rat Model of Major Depressive Disorder.
journal, 2023 - [djillani-2017]Djillani 2017 — Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity.
journal, 2017 - [ma-2020]Ma 2020 — Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels.
journal, 2020 - [mazella-2018]Mazella 2018 — The Involvement of Sortilin/NTSR3 in Depression as the Progenitor of Spadin and Its Role in the Membrane Expression of TREK-1.
journal, 2018 - [nasr-2018]Nasr 2018 — Identification and characterization of two zebrafish Twik related potassium channels, Kcnk2a and Kcnk2b.
journal, 2018 - [pietri-2019]Pietri 2019 — First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides.
journal, 2019 - [qi-2018]Qi 2018 — Comparison of Therapeutic Effects of TREK1 Blockers and Fluoxetine on Chronic Unpredicted Mild Stress Sensitive Rats.
journal, 2018 - [wu-2021]Wu 2021 — Genetic and pharmacological inhibition of two-pore domain potassium channel TREK-1 alters depression-related behaviors and neuronal plasticity in the hippocampus in mice.
journal, 2021