PE-22-28
Also known as: PE 22-28, spadin analog (7-mer), shortened spadin analog
Endogenous peptide analog / TREK-1 channel blocker
What it is
PE-22-28 is a 7-amino-acid peptide derived from the study of blood degradation products of spadin (PE 12-28). It specifically blocks the TREK-1 potassium channel with an IC50 of 0.12 nM, displaying better specificity and affinity for TREK-1 compared to its parent peptide spadin (IC50 40–60 nM for spadin). TREK-1 inhibition is associated with antidepressant activity. PE-22-28 and its derivatives also promote neurogenesis after short (4-day) treatment and enhance synaptogenesis as measured by increased PSD-95 expression in mouse cortical neurons.
Class: Endogenous peptide analog / TREK-1 channel blocker
What it's studied for
- Antidepressant activity Animal studies only
- PE-22-28 and its derivatives demonstrated antidepressant properties in the forced swimming test (significant reduction in immobility time in mice) and in the novelty suppressed feeding test (significant reduction in latency to eat after 4-day sub-chronic treatment). Action duration was up to 23 h, compared to 7 h for s PMID 28955242 Djillani et al., Frontiers in Pharmacology (2017)
- TREK-1 channel inhibition Mixed
- In vitro patch-clamp studies on hTREK-1/HEK cells showed PE-22-28 has an IC50 of 0.12 nM for TREK-1, significantly better than spadin (IC50 40–60 nM). Modifications to N- or C-terminal ends could maintain or abolish TREK-1 channel activity without affecting PE-22-28 affinity. PMID 28955242 Djillani et al., Frontiers in Pharmacology (2017)
- Neurogenesis induction Animal studies only
- PE-22-28 and its analogs were able to induce neurogenesis after only a 4-day treatment in vivo, with a prominent effect observed for the G/A-PE 22-28 derivative. PMID 28955242 Djillani et al., Frontiers in Pharmacology (2017)
- Synaptogenesis enhancement In vitro only
- On mouse cortical neurons, PE-22-28 and its derivatives enhanced synaptogenesis as measured by an increase in PSD-95 expression level. PMID 28955242 Djillani et al., Frontiers in Pharmacology (2017)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Not explicitly stated in the abstract | Not explicitly stated in the abstract for in vivo dosing; sub-chronic treatment described as 4-day regimen | 4 days (sub-chronic) | animal | Research PMID 28955242 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- No specific safety signals or adverse effects for PE-22-28 are reported in the reviewed abstract; the parent compound spadin is noted to have 'serious adverse effects' associated with existing antidepressants as a class context, but no specific adverse effects are attributed to PE-22-28 itself. PMID 28955242
Frequently asked
What is PE-22-28 and how does it work?
PE-22-28 is a 7-amino-acid peptide analog derived from spadin (PE 12-28), designed by studying spadin's blood degradation products. It works by selectively blocking the TREK-1 potassium channel with an IC50 of 0.12 nM — significantly more potent than spadin (IC50 40–60 nM). TREK-1 inhibition is linked to antidepressant effects. PE-22-28 also promotes neurogenesis and synaptogenesis in preclinical models.
Has PE-22-28 been tested in humans?
Based on the available reviewed literature, PE-22-28 has only been studied in vitro (hTREK-1/HEK cells, mouse cortical neurons) and in animal models (mice). No human clinical trials are described in the reviewed abstracts.
What dose of PE-22-28 should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: the available abstract describes a 4-day sub-chronic treatment in mice but does not specify the exact dose or route of administration used in vivo. No human dosing data exist in the reviewed literature.
How long does PE-22-28 last compared to spadin?
According to the reviewed literature, PE-22-28 and its analogs had an action duration of up to 23 hours, compared to 7 hours for the parent peptide spadin. This improvement was a key motivation for developing shortened spadin analogs.
Can PE-22-28 treat depression?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. What the preclinical research has shown: PE-22-28 demonstrated antidepressant-like properties in mouse behavioral models (forced swimming test, novelty suppressed feeding test) and promoted neurogenesis after 4-day treatment, but no human clinical evidence is available in the reviewed literature.
What is the difference between PE-22-28 and spadin?
PE-22-28 is a shortened 7-amino-acid analog of spadin (PE 12-28), designed to improve stability and bioavailability. Key differences reported in preclinical research: PE-22-28 has a much lower IC50 for TREK-1 (0.12 nM vs. 40–60 nM for spadin), and a longer action duration (up to 23 h vs. 7 h for spadin).
Can I stack PE-22-28 with an antidepressant?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: PE-22-28 has demonstrated antidepressant-like effects via TREK-1 inhibition in preclinical mouse models. No combination or stacking studies are described in the reviewed literature.
Where can I buy PE-22-28?
I don't recommend vendors or sources. Please consult a licensed provider.
Is PE-22-28 approved by the FDA?
The reviewed literature does not state any regulatory approval status for PE-22-28 by the FDA or any other regulatory body. Please verify current regulatory status through official sources such as the FDA website or consult a licensed healthcare provider.
What are the side effects of PE-22-28?
I don't have reliable study data on that specific question. The reviewed abstract does not report any adverse effects or safety signals specific to PE-22-28. All studies described are preclinical (animal/in vitro). I won't guess — please consult a licensed provider or peer-reviewed literature directly.
References
- [1] PMID 28955242 — PE-22-28 and its derivatives demonstrated antidepressant properties in the forced swimming test (significant reduction in immobility time in mice) and in the no