PE-22-28 (Mini-Spadin)
TREK-1 Channel Blocker | Shortened Spadin Analog
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What is PE-22-28 (Mini-Spadin)?
PE-22-28 (Mini-Spadin) is a small lab-made peptide, just seven amino acids, designed to block a specific potassium channel (TREK-1) that researchers have linked to mood regulation. In animal studies it's been studied for how quickly it appears to affect mood-related behavior compared to standard antidepressant research compounds. Research-grade PE-22-28 sold here is intended strictly for laboratory study, not for use in people or animals — there have been no human clinical trials.
Key terms:
PE-22-28 (Mini-Spadin) is a synthetic linear heptapeptide.
PE-22-28, also known as Mini-Spadin, is a lab-made peptide of seven amino acids. Its sequence comes from positions 22-28 of the parent peptide Spadin. Spadin itself originates from the propeptide (PE) released when sortilin/neurotensin receptor-3 (NTSR3) matures. PE-22-28 is a potent, selective antagonist (blocker) of TREK-1, the TWIK-Related Potassium Channel-1. That two-pore domain potassium channel is implicated in depression, neuroprotection, and pain modulation. With an IC50 of 0.12 nM, PE-22-28 binds TREK-1 roughly 300-500 fold more tightly than full-length Spadin. In preclinical research, antidepressant effects appeared within 4 days, alongside neurogenesis and synaptogenesis (new nerve cells and new connections) in the hippocampus — significantly faster than conventional SSRIs.
Key research areas
- Rapid antidepressant-like effects (4 days in preclinical models)
- Hippocampal neurogenesis
- Synaptogenesis (PSD-95 increase)
- CREB activation
- Enhanced serotonergic neurotransmission
- Extended duration of action (~23 hours)
Researched dosing
This table shows the animal-study dosing used in published PE-22-28 research, alongside theoretical human-equivalent research ranges — presented as research reference, not personal usage guidance.
| Phase | Dose | Frequency | Route |
|---|---|---|---|
| Preclinical mouse studies | 3-4 mcg/kg | Once daily | Intraperitoneal (IP) |
| Preclinical oral mouse studies | 1 mg/kg | Once daily | Oral gavage |
| Theoretical human-equivalent dose | 50-100 mcg | Once daily | Subcutaneous |
| Lower-dose study protocol | 100-200 mcg | Once daily | Subcutaneous |
Commonly cycled 8 weeks on, 2+ weeks off.
How it works
At the cell level, PE-22-28 research looks at how the peptide blocks TREK-1, a potassium channel, which in animal models increases activity in mood-related brain circuits and raises BDNF levels — the terms below describe those signaling steps.
PE-22-28 selectively blocks TREK-1 potassium channels with IC50 of 0.12 nM. TREK-1 inhibition increases neuronal excitability in the dorsal raphe nucleus, enhancing serotonin (5-HT) firing rate and neurotransmission. This triggers downstream CREB phosphorylation, BDNF expression, and hippocampal neurogenesis. Unlike SSRIs that take weeks, these effects manifest within 4 days in animal models.
Molecular data
These figures — molecular weight, sequence, chain length — are the chemistry ID researchers use to confirm a PE-22-28 sample's identity; at just seven amino acids, it's a shortened version of a larger parent peptide called Spadin.
- Weight
- 773.89 Da
- Length
- 7 amino acids
- Type
- Linear heptapeptide
Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)
Research applications
This section lists the research areas — mood, cognitive, and anxiety research among them — that scientists have studied for PE-22-28 in animal models; all of this data comes from preclinical research, with no human clinical trials conducted.
Mood
Primary research focus. Preclinical studies show rapid antidepressant effects in forced swim test, tail suspension test, learned helplessness, and novelty-suppressed feeding models. Acts faster than SSRIs with 4-day efficacy window. PE-22-28 nearly doubles hippocampal BrdU-positive (newborn) cells after 4-day treatment. 85% of new cells are neuronal precursors (DCX-positive), indicating genuine neuroplasticity.
Cognitive
Enhanced cognitive function via neuroplasticity, BDNF expression, and direct hippocampal neurogenesis support memory and learning.
Anxiety
Preclinical data suggests anxiolytic-like effects through serotonergic and TREK-1 modulation pathways.
Neuroprotection
Potential neuroprotection through TREK-1 inhibition and BDNF upregulation.
Dosage reference
- Doses used in research
- 50–200 mcg (research context)
- Frequency in studies
- Once daily
- Handling
- Reconstituted solution — research use only; not for administration
- Timeline reported in studies
- Days 1-4: Preclinical models show measurable antidepressant effects by day 4; Weeks 1-2: Neurogenesis and synaptogenesis established; Weeks 2-4: Continued neuroplasticity and mood effects
- Storage
- Lyophilized: refrigerate 2-8°C or -20°C for long-term; Reconstituted: refrigerate, use within 4-6 weeks
- Cycle length
- 4-8 weeks typical research protocol
- Break between cycles
- Limited data on cycling; some protocols suggest 4 weeks on, 2-4 weeks off
Interactions
This list shows which other mood- and cognitive-research compounds are studied alongside PE-22-28, and why some pairings call for extra caution.
Reconstitution & storage
This is the standard laboratory method for turning freeze-dried PE-22-28 powder into a liquid research solution.
- Remove PE-22-28 vial from refrigerator and allow to reach room temperature
- Clean the rubber stopper with alcohol swab
- Determine reconstitution volume (e.g., 2 mL BAC water for 10 mg vial = 5 mg/mL or 5000 mcg/mL)
- Draw bacteriostatic water into syringe slowly
- Inject BAC water slowly down the inside wall of the vial - do not spray directly on powder
- Gently swirl vial until powder is completely dissolved - do not shake
- Solution should be clear and colorless
- Label vial with reconstitution date and concentration
Lyophilized: 2-8°C or -20°C for long-term, use within Per manufacturer expiration date
Reconstituted: 2-6°C, use within 4-6 weeks
Open the PE-22-28 reconstitution calculatorQuality indicators
These are the checks researchers use to confirm a PE-22-28 sample is pure and correctly identified — especially important given how little clinical-grade sourcing exists for this compound.
White lyophilized powder - Should appear as white to off-white powder or fluffy cake in sealed vial
Clear, colorless reconstituted solution - After reconstitution, solution must be completely clear with no particles or cloudiness
Certificate of Analysis (COA) available - Research peptide should have third-party testing showing >98% purity and identity confirmation via HPLC/MS
Proper cold chain shipping - Should arrive cold-packed; extended room temperature exposure may degrade peptide
Research compound status - PE-22-28 is not FDA-approved. Available only as research chemical. Quality varies by supplier
Cloudy, discolored, or particles visible - Any turbidity, yellow/brown color, or floating particles indicates degradation
Clumped or sticky powder - Indicates moisture exposure and likely degradation - do not use
What to expect
This timeline reflects what the preclinical research literature reports at each study stage — research context for comparing animal studies, not a personal-results promise; human timelines are unknown.
Preclinical data suggests measurable effects within 4 days; subjective effects in humans unknown
Based on mechanism, expect neuroplasticity processes to be underway
If effective, mood and cognitive improvements may become noticeable
Sustained use allows full neurogenic effects to develop
Safety notes
This section covers handling cautions for PE-22-28 — all safety data comes from animal studies, research-use-only scope, not medical safety advice for people.
- NOT FDA-approved - research compound only with no human clinical trials
- All safety data is from preclinical (animal) studies
- Theoretical serotonin syndrome risk if combined with MAOIs or high-dose SSRIs - avoid combination
- Long-term safety in humans completely unknown
- Not recommended during pregnancy or breastfeeding (no safety data)
- Start with lowest effective dose; do not exceed research protocol ranges
- Not FDA-approved - research chemical only with no human clinical trials
Regulatory status
- Not approved by the FDA for any indication.
- Supplied and described for laboratory research use only — not for human or veterinary use.
Community data
Community Insights
Based on data the community reported. Not clinical proof.
Frequently asked questions
What is PE-22-28 studied for in research?
PE-22-28 (Mini-Spadin) is a synthetic heptapeptide and a selective TREK-1 potassium-channel blocker derived from Spadin. Preclinical rodent research has examined it for rapid neuroplasticity signaling — hippocampal neurogenesis and BDNF pathways — in mood-related models. It is supplied strictly as a research-use-only reference material, not for human use.
How is PE-22-28 reconstituted for laboratory use?
Bring the vial to room temperature and wipe the stopper with alcohol. Draw bacteriostatic water — for example 2 mL into a 10 mg vial gives 5 mg/mL — and inject it slowly down the inside wall. Swirl gently until clear and colorless, never spraying onto the powder, then label the vial.
How should PE-22-28 be stored?
Lyophilized PE-22-28 is stored at 2-8°C, or -20°C for long-term holding, protected from light. After reconstitution the solution is kept near 2-6°C and used within about 4-6 weeks. Cold, dark storage limits degradation of the heptapeptide across the study window, and cloudy solutions are discarded.
How does PE-22-28 differ from Selank?
Both are short peptides studied in mood and neuroprotection research, but by different mechanisms: PE-22-28 selectively blocks TREK-1 potassium channels to raise serotonergic firing, while Selank is a tuftsin-derived peptide studied for GABAergic and anxiolytic-type signaling. They are distinct research reference compounds.
References
Revealed Spadin and analogs specifically antagonize arachidonic acid-mediated TREK-1 activation via allosteric mechanism. This selective inhibition may explain favorable side effect profile compared to non-specific K+ channel blockers.
Review establishing TREK-1's role in depression, neuroprotection, pain, and anesthesia. TREK-1 is highly expressed in prefrontal cortex, hippocampus, and amygdala - regions critical for mood and memory. Supports TREK-1 blockers as novel therapeutic approach.
Comprehensive review of TREK-1 as depression target and Spadin development. Highlighted rapid onset of action (4 days vs weeks for SSRIs), neurogenesis induction, and favorable safety profile in preclinical studies.