Mind & sleep

PE-22-28 (Mini-Spadin)

Shortened spadin analogue

No FDA-approved product identified for this exact research entry in the targeted review.

What does it do?

PE-22-28 is a spadin-derived peptide investigated as a TREK-1 blocker. Cell and mouse experiments do not establish an antidepressant treatment in people.

Experimental antidepressant mechanism

The seven-residue peptide blocked TREK-1 in cells and reduced depression-like behavior in mouse assays. This does not show that it treats depression in people.1

Compare doses by goal

Molecular information

1 16

Amino-acid sequence

7 residues · N → C16

Reference identity · not independently confirmed16

Length7 amino acids

Molecular weight · Da773.89 Da

Molecular formulaNot independently verified1 16

Identity reported by Pep-Pedia; exact-product sequence and modifications have not been independently confirmed.

Distinguish PE 22–28 from G/A and biotinylated derivatives.

How long does it stay in the body?

Pharmacokinetics · How quickly the compound clears.

Half-lifeHuman half-life not verified1

The study measured mouse behavioral effect duration, including modified derivatives, not human plasma elimination.

There is not enough numerical information in the checked sources to show a clearance curve.

What to expect

Study outcomes

Channel and mouse-behavior evidence

Human efficacy, dosing and adverse effects are not established by this preclinical study.1

Reported timelines

Reference & community

Animal findings

Antidepressant-like activity within four days; source extrapolates 1–8-week plasticity changes.16

Human expectations

No validated timeline, particularly oral or nasal.16

These are reported timelines, not a prediction of your response.

Doses by goal

These are reported practices from secondary sources, not validated dosing recommendations.

Route

Scroll to compare all columns →

One row for each documented route and dose or dose range
Goal	Dose	Frequency	Route	Duration	Source
Research Protocol (Human Equivalent - Theoretical)	50-100 mcg	Once daily	SubQ	4-8 weeks typical research protocol	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Injectable
Research Protocol (Conservative)	100-200 mcg	Once daily	SubQ	4-8 weeks typical research protocol	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Injectable
Research Protocol (Theoretical)	100-300 mcg	Once or twice daily	IntranasalNasal spray	Not specified	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Nasal

Cycles & timing

Reference reports16

Reported use periods and breaks. These do not establish a safe cycle or prove that breaks prevent tolerance.

Injectable

Use period: 4-8 weeks typical research protocol
Break: Limited data on cycling; some protocols suggest 4 weeks on, 2-4 weeks off

Reported timing

Morning administration common; ~23 hour duration of action supports once-daily dosing

Oral

Use period: Not established
Break: Not established

Reported timing

Not established

Nasal

Use period: Not established
Break: Not established

Reported timing

Morning administration typical for nootropic peptides

Animal and cell protocols 3

Laboratory exposures cannot establish a human dose.

These are reported practices from secondary sources, not validated dosing recommendations.

Route

Scroll to compare all columns →

Animal and cell exposures
Goal	Dose	Frequency	Route	Duration	Source
Preclinical Antidepressant Studies (Mouse)	3-4 mcg/kg	Once daily	OtherIP	4-8 weeks typical research protocol	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Injectable
Preclinical Oral Studies (Mouse)	1 mg/kg	Once daily	OralOral gavage	4-8 weeks typical research protocol	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Injectable
Preclinical Oral Study (Mouse)	1 mg/kg	Once daily	OralOral gavage	Not specified	16
Population Population not independently verified; see the reference and linked research. Context Reported in Pep-Pedia’s educational protocol table. Study attribution and applicability to this exact product are not independently established. Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims. Source tabs Oral

Side effects & safety

Evidence limitation

Mouse behavioral effects are not a human safety assessment.

Evidence limitation

Activity duration of modified analogues is not PE-22-28 human pharmacokinetics.

Additional reported cautions

Reference reports16

Unknown safety

No human trials or established oral/nasal exposure.

Urgent

Agitation, confusion, tachycardia, hypertension or twitching may indicate serotonergic toxicity; seizures, chest pain, allergy, mania/suicidal thoughts or unusual bleeding need assessment.

Local

Persistent nasal bleeding, irritation or infection.

Not a complete safety screen. Discuss health decisions with a qualified clinician.

Combinations & interactions

9 entries

Check cautions and reported pairings. A compatibility claim does not establish that a combination is safe.

SSRIs

Caution reported

Theoretical serotonergic excess.16

Reference report · Pep-Pedia label: Monitor Combination

Potassium-channel drugs

Caution reported

Potential channel interactions.16

Reference report · Evidence context: Use caution

MAOIs

Avoidance reported

Theoretical serotonin toxicity.16

Reference report · Pep-Pedia label: Avoid Combination

Semax / NA-Semax

Unverified pairing

Unstudied plasticity pairing.16

Reference report · Evidence context: Potentially synergistic

Selank

Unverified pairing

Unstudied pairing.16

Reference report · Pep-Pedia label: Synergistic

Dihexa

Unverified pairing

Unstudied growth signaling.16

Reference report · Evidence context: Potentially synergistic

Cerebrolysin

Unverified pairing

Unstudied pairing.16

Reference report · Pep-Pedia label: Compatible

BPC-157

Unverified pairing

Unstudied pairing.16

Reference report · Pep-Pedia label: Compatible

Other medicines or peptides

Not established

No exact-product human interaction study was verified; lack of evidence is not evidence of safety.2

Research context

Reconstitution

No validated preparation identified

No product-specific preparation or stability instruction was verified. A dilution calculation does not establish suitability for injection.2

Reference preparation details

Reported handling information, not a validated formulation or instruction to prepare an injectable product.

Injectable

The source gives a 10 mg vial example.

Solvents mentioned: Bacteriostatic water
Reported parameters: 10 mg in 2 mL gives 5 mg/mL. · Reported storage: 2–8°C for 4–6 weeks.

The source describes gentle mixing and avoiding vigorous shaking.

Oral

The oral view contains only a generic injection banner and no route-specific preparation information.

No oral solvent or mixing protocol can be inferred from that banner.

Nasal

Pep-Pedia describes preparation for this route; product-specific stability has not been independently verified.

Solvents mentioned: Bacteriostatic water
Reported parameters: The source specifies refrigeration after preparation.

Appearance & documentation

Appearance and a purity certificate cannot establish sterility, identity, or suitability for injection.

Reported appearanceWhite lyophilized powderReported appearanceClear, colorless reconstituted solutionReported appearanceCertificate of Analysis (COA) availableReported appearanceProper cold chain shippingReported variationResearch compound statusReported concernCloudy, discolored, or particles visibleReported concernClumped or sticky powder

Available forms

No verified packaging examples included.

Packaging examples, not a market survey. Approved and research products are not interchangeable.

Storage after mixing

Reconstituted research vials

Pep-Pedia reports these handling limits after mixing. They are not validated stability or sterility limits for your vial.

Injectable

Unverified report16

Refrigerated; temperature not specified · 4–6 weeks

Storage notes

Injectable

Lyophilized: refrigerate 2-8°C or -20°C for long-term; Reconstituted: refrigerate, use within 4-6 weeks

Oral

Refrigerate solution; protect from light

Nasal

Refrigerate reconstituted solution

Storage depends on the formulation, diluent, container, and handling. Follow the specific product label or pharmacist’s instructions.

Evidence limits

View findings →

Human efficacy, dosing and adverse effects are not established by this preclinical study.1

Early research. The relevant evidence is mainly from cells or animals. Human biomarker associations do not show what happens when people take the compound.

Evidence definitions →

Research findings

Preclinical

Source context

Animal cardiac selectivity does not establish human cardiac safety; combination labels are source claims.

Compound identity & other names

PE-22-28 is a spadin-derived peptide investigated as a TREK-1 blocker. Cell and mouse experiments do not establish an antidepressant treatment in people.

No FDA-approved product identified for this exact research entry in the targeted review.

Shortened spadin analogue PE 22–281 16

Pep-Pedia identity record

7 amino acids · 773.89 Da

Gly-Val-Ser-Trp-Gly-Leu-Arg (GVSWGLR)

Reference description; checked chemical identity takes precedence when available.16

How it may work

TREK-1 blockade alters neuronal excitability, serotonin signaling and downstream plasticity.16

Channel and mouse-behavior evidence

The seven-residue peptide blocked TREK-1 in cells and reduced depression-like behavior in mouse assays. This does not show that it treats depression in people.

Research areas and evidence gaps

Experimental antidepressant mechanism. The seven-residue peptide blocked TREK-1 in cells and reduced depression-like behavior in mouse assays. This does not show that it treats depression in people.1

Human efficacy, dosing and adverse effects are not established by this preclinical study.
A product-specific research-vial quantity was not independently verified in this review.

Additional uses listed by Pep-Pedia

Mood / anxiety. Depression, anxiety and neurogenesis models.16

Cognition / protection. Memory and stroke-related neuroprotection hypotheses.16

Routes. Oral animal activity; nasal delivery remains theoretical.16

Community reports Unvalidated

Pep-Pedia discusses preclinical depression research.2

Editorial summary, not a measured community survey, clinical protocol or recommendation.

Search coverage and review status

No newer human clinical study was verified. Checked the original cell and mouse paper; behavioral duration is not human elimination half-life.

Checked: 2026-10-12
Search: "PE-22-28" 2025 2026 study
Catalog: Pep-Pedia ↗ · 13 listed references retained

Targeted search and selected primary-source checks, not an exhaustive systematic review.
Preserved bibliography entries marked unreviewed have not had their findings independently verified.

AI-prepared summaries. Independent medical editorial review is pending.

Community poll 10 topics · Pep-Pedia snapshot

Voluntary, unverified reports. These percentages do not measure effectiveness or safety.

Topic

Primary goal

Cognitive enhancement52%

General wellness22%

Other: Depression7%

Other: Depression 4%

Other: Depression/ anxiety 4%

The source hides 3 additional categories. Their labels and percentages are unavailable.

Number of responses to this question: not disclosed.

Source & limitations

The source displays “296 responses” for this profile. This is not a confirmed participant count or a denominator for individual questions.

Voluntary self-reports from Pep-Pedia visitors; identity, treatment, outcomes and timing are unverified. These data are not efficacy or safety estimates.
The source displays a profile-wide response label, not a confirmed unique participant count. It stays unchanged across questions. Question-specific denominators and absolute option counts are not exposed.
Only the top five categories are displayed for some questions. Extra categories are retained as an undisplayed-category count; their labels and percentages are unavailable.
Displayed percentages are rounded. They may not total 100%, especially where categories are hidden.
This is a dated snapshot, not a live survey or current recommendation.

References

Original sources and review status. Open a reference to read its summary.

16 sources

1Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant ActivityPreclinical · 2017 · frontiersin.orgPrimary source checked

AI-PREPARED SUMMARY

PE 22-28 inhibited TREK-1 in cells and changed depression-like behavior in mice. Longer activity measurements concerned modified analogues, not human elimination.

Channel and mouse-behavior evidence

The seven-residue peptide blocked TREK-1 in cells and reduced depression-like behavior in mouse assays. This does not show that it treats depression in people.

Additional research · Checked 2026-10-12

Original source

2Pep-Pedia: PE-22-28 (Mini-Spadin)Community · Accessed 2026 · pep-pedia.orgCommunity source checked

AI-PREPARED SUMMARY

Secondary editorial profile and reported practices; not clinical validation.

Original source

3Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1Reference · Accessed 2026 · frontiersin.orgPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: Spadin-related compounds selectively interfered with arachidonic-acid activation of TREK-1; mechanism does not establish clinical tolerability.

Reported population / model
Frontiers in Pharmacology 2020

Reported study details
Mechanism of action study

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

4Role of TREK-1 in Health and Disease - CNS FocusReference · Accessed 2026 · pmc.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The review describes TREK-1 roles in mood, pain, neuroprotection and anesthesia; target biology is not proof of peptide-treatment efficacy.

Reported population / model
Frontiers in Physiology 2019

Reported study details
Comprehensive review · Multiple disease states

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

5Fighting Against Depression with TREK-1 BlockersReference · Accessed 2026 · sciencedirect.comPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The review describes rapid behavioral and neurogenesis effects in preclinical spadin experiments; comparison with antidepressant onset is not a human trial.

Reported population / model
Pharmacology & Therapeutics 2019

Reported study details
Review of Spadin research

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

6Shortened Spadin Analogs Display Better TREK-1 InhibitionReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The source reports stronger channel inhibition and longer animal effects for shortened analogues; four-day treatment increased neurogenesis markers.

Reported population / model
Frontiers in Pharmacology 2017

Reported study details
In vitro and in vivo studies · Mice models

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

7Spadin: A Sortilin-Derived Peptide Targeting TREK-1 ChannelsReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: Parent spadin produced CREB and hippocampal-neurogenesis changes in animal depression models; this is not direct clinical PE-22-28 evidence.

Reported population / model
PLOS Biology 2010

Reported study details
Original spadin discovery · Multiple depression models

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

8TREK-1 Deletion Results in Depression-Resistant PhenotypeReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: TREK-1 knockout mice showed altered stress/depression-like behaviors and serotonin signaling; genetic deletion is not a tested human therapy.

Reported population / model
Nature Neuroscience 2006

Reported study details
TREK-1 knockout mice · Behavioral and electrophysiology

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

9Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant ActivityReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The source reports stronger channel inhibition and longer animal effects for shortened analogues; four-day treatment increased neurogenesis markers.

Reported population / model
Frontiers in Pharmacology 2017

Reported study details
In vitro and in vivo studies · Mice models

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

10Spadin targeting rodent TREK-1 channels: new antidepressant drug designReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: Parent spadin produced CREB and hippocampal-neurogenesis changes in animal depression models; this is not direct clinical PE-22-28 evidence.

Reported population / model
PLOS Biology 2010

Reported study details
Original spadin discovery · Multiple depression models

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

11Deletion of background potassium channel TREK-1 produces depression-resistant phenotypeReference · Accessed 2026 · pubmed.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: TREK-1 knockout mice showed altered stress/depression-like behaviors and serotonin signaling; genetic deletion is not a tested human therapy.

Reported population / model
Nature Neuroscience 2006

Reported study details
TREK-1 knockout mice · Behavioral and electrophysiology

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

12Fighting against depression with TREK-1 blockers: a focus on spadinReference · Accessed 2026 · sciencedirect.comPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The review describes rapid behavioral and neurogenesis effects in preclinical spadin experiments; comparison with antidepressant onset is not a human trial.

Reported population / model
Pharmacology & Therapeutics 2019

Reported study details
Review of Spadin research

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

13Spadin selectively antagonizes arachidonic acid activation of TREK-1 channelsReference · Accessed 2026 · frontiersin.orgPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: Spadin-related compounds selectively interfered with arachidonic-acid activation of TREK-1; mechanism does not establish clinical tolerability.

Reported population / model
Frontiers in Pharmacology 2020

Reported study details
Mechanism of action study

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

14Role of TREK-1 in Health and Disease, Focus on CNSReference · Accessed 2026 · pmc.ncbi.nlm.nih.govPep-Pedia report · Primary source not checked

AI-PREPARED SUMMARY

Pep-Pedia reports: The review describes TREK-1 roles in mood, pain, neuroprotection and anesthesia; target biology is not proof of peptide-treatment efficacy.

Reported population / model
Frontiers in Physiology 2019

Reported study details
Comprehensive review · Multiple disease states

Reported by Pep-Pedia; the linked publication, design, doses and result have not been independently verified here.

Read the Pep-Pedia report ↗

Pep-Pedia reference card; original summary of its reported findings · Checked 2026-10-12

Listed study

15Blocking TREK-1 inhibits A1-like reactive astrocytes through NF-kB in rat depression modelReference · Accessed 2026 · link.springer.comLinked reference · Not independently reviewed

REFERENCE NOTE

Reference retained from Pep-Pedia’s bibliography; findings and bibliographic accuracy have not been independently verified.

Pep-Pedia bibliography · Checked 2026-10-12

Listed source

16Pep-Pedia: PE-22-28 (Mini-Spadin) — route-specific referenceReference page checked; underlying claims require separate verification.Community · Checked 2026 · pep-pedia.orgCommunity source checked

AI-PREPARED SUMMARY

Source page checked across available routes. Protocols, cycles, storage, mechanisms and pairing claims are secondary reports; checking the page does not independently validate those claims. Original concise summaries are used here.

Content coverage audit · Checked 2026-10-12

Original source

What does it do?

Experimental antidepressant mechanism

Molecular information

Amino-acid sequence

How long does it stay in the body?

What to expect

Study outcomes

Channel and mouse-behavior evidence

Reported timelines

Animal findings

Human expectations

Doses by goal

Cycles & timing

Injectable

Reported timing

Oral

Reported timing

Nasal

Reported timing

Side effects & safety

Evidence limitation

Evidence limitation

Additional reported cautions

Unknown safety

Urgent

Local

Combinations & interactions

SSRIs

Potassium-channel drugs

MAOIs

Semax / NA-Semax

Selank

Dihexa

Cerebrolysin

BPC-157

Other medicines or peptides

Reconstitution

Reference preparation details

Injectable

Oral

Nasal

Appearance & documentation

Available forms

Storage after mixing

Reconstituted research vials

Injectable

Storage notes

Evidence limits

Research findings

Source context

Pep-Pedia identity record

How it may work

Channel and mouse-behavior evidence

Research areas and evidence gaps

Additional uses listed by Pep-Pedia

Community reports Unvalidated

Experience

Duration of use

Age range

Gender

Primary goal

Effectiveness

Side effects

Dosage frequency

Would recommend

How discovered

References