Research monograph

PE-22-28[A shortened spadin analogue]

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Compound snapshot

Class

Research peptide

FDA approved

Clinical development

Phase 2

Last reviewed

September 2026

Research areas

Cognition / Mood / Neuroprotection

Regulatory status

Research use only — not approved

Internet attention

Moderate

Registry query

PE-22-28

A seven-amino-acid experimental fragment designed from spadin, an endogenous sortilin-derived peptide. It is studied as a possible fast-acting antidepressant lead, not as an established mental-health treatment.

Reality check — what we actually know

Supported by human evidence

No adequately powered randomised human trials establish the outcomes this compound is marketed for.

Animal research only

Showed substantially stronger TREK-1 binding in cell studies than the parent peptide spadin
Reduced immobility in mouse behavioural tests used to screen antidepressant-like activity
Was designed for improved stability and duration compared with parent spadin

Mechanistically plausible

Blocks the TREK-1 two-pore potassium channel. In preclinical models, TREK-1 inhibition alters neuronal excitability and is associated with serotonergic signalling and hippocampal neurogenesis.

Common internet claims

Online discussion frequently presents PE-22-28 as a proven treatment rather than a research compound.

Not established

Human efficacy for the outcomes commonly claimed
Optimal route, quantity and duration in humans
Long-term human safety

Evidence distribution

Each band is a live PubMed search for PE-22-28, filtered to that kind of study. Top is the strongest evidence; the base is reasoning, not proof. A band with no records means that kind of study has not been published for this compound yet.

Meta-analyses…Randomised trials…Human studies…Animal studies…Cell and laboratory data…Mechanistic theory…

Mechanism and reported findings

Blocks the TREK-1 two-pore potassium channel. In preclinical models, TREK-1 inhibition alters neuronal excitability and is associated with serotonergic signalling and hippocampal neurogenesis.

Showed substantially stronger TREK-1 binding in cell studies than the parent peptide spadin
Reduced immobility in mouse behavioural tests used to screen antidepressant-like activity
Was designed for improved stability and duration compared with parent spadin
Provides a research tool for exploring TREK-1 as an antidepressant target

Strength of the evidence: Preclinical only. Findings come from cells and rodent behavioural models, largely from one research group. There are no published human trials and no evidence that it treats clinical depression.

Safety and known cautions

Human safety, interactions and psychiatric effects are unknown. Animal screening tests do not establish antidepressant effectiveness. Depression and suicidal thoughts require prompt care from a qualified professional, not a research chemical.

Evidence at a glance

No single score, on purpose. The line beside each bar shows how much reported outcomes vary between studies.

Human studiesLimited

Animal studiesMultiple studies

Lab / in-vitroMultiple studies

Clinical efficacyNot established

Long-term safetyNot established

Development stage

Discovery
Preclinical
Phase 1
Phase 2Current
Phase 3
Regulatory review
Approved

Registered trials on ClinicalTrials.gov →

Primary sources

PubMed / NCBI

Published research on PE-22-28

ClinicalTrials.gov

Registered trial records

WHO ICTRP

International trial registries

FDA

Bulk drug substances and compounding safety

Education only — research summary, not dosing advice. Approved medicines are prescription-only; investigational compounds are not approved for human use.