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Cognitive

PE-22-28

GVSWGLR, a shortened spadin/sortilin-derived TREK-1 antagonist peptide

Experimental TREK-1 antagonist peptide research focused on neuroplasticity and mood-related pathways.

Preclinical Evidence

Route

Subcutaneous in the community educational protocol

Common format

10 mg vial

Research focus

TREK-1

Evidence level

Preclinical Evidence

Typical cycle

No established human cycle

Cognitive research motifCognitive

PE-22-28 in 30 seconds

Atlas Fast Read

What it is

GVSWGLR, a shortened spadin/sortilin-derived TREK-1 antagonist peptide

Why people care

Experimental TREK-1 antagonist peptide research focused on neuroplasticity and mood-related pathways.

Human evidence

Preclinical Evidence — The exact compound or use is supported mainly by animal, in-vitro, or mechanistic work, or lacks meaningful controlled human efficacy evidence.

Biggest misconception

Key gaps include validated human dosing, pharmacokinetics, long-term safety, clinically meaningful efficacy, product standardization, and independent replication in well-controlled trials.

Bottom line

PE-22-28 is scientifically interesting for TREK-1, depression models, but the current case is driven mainly by cell and animal data.

Overview

What is PE-22-28?

PE-22-28 is gVSWGLR, a shortened spadin/sortilin-derived TREK-1 antagonist peptide. Experimental TREK-1 antagonist peptide research focused on neuroplasticity and mood-related pathways.

PE-22-28 was developed in the 2010s from spadin, a sortilin-derived peptide that inhibits TREK-1 potassium channels. Shortened analogues were engineered to improve potency and duration in antidepressant and neuroprotection models.

Mechanism

How it works

Potently inhibits TREK-1 two-pore potassium channels, increasing neuronal excitability and downstream serotonergic/neuroplastic signaling. Animal studies report rapid changes in neurogenesis and synaptic markers.

Research areas

TREK-1depression modelsneurogenesisstroke recovery

Evidence

What does the evidence actually say?

Preclinical Evidence

The exact compound or use is supported mainly by animal, in-vitro, or mechanistic work, or lacks meaningful controlled human efficacy evidence.

01

Preclinical Evidence

02

Limited Human Evidence

03

Strong Human Evidence

Human evidence

No human trials establish PE-22-28 for depression, neurogenesis, or stroke recovery. Its evidence is preclinical.

Preclinical evidence

Rodent studies report TREK-1 inhibition, rapid antidepressant-like behavior, neurogenesis, and neuroprotection after ischemic injury. No human translation has yet been demonstrated.

Knowledge gaps

Key gaps include validated human dosing, pharmacokinetics, long-term safety, clinically meaningful efficacy, product standardization, and independent replication in well-controlled trials.

Protocol

Research protocol

DoseFrequencyTimingCycle

Dose

Community research reference: 50–200 mcg/day. There is no human dose because human trials have not established safety or efficacy.

Frequency

Once daily in the community experimental protocol.

Timing

No established time-of-day requirement.

Route

Subcutaneous in the community educational protocol; published efficacy evidence is preclinical.

Cycle length

No established human cycle

Reconstitution

Community reference: 1 mL bacteriostatic water per 10 mg vial = 10 mg/mL.

Storage

Community reference: lyophilized frozen; reconstituted 2–8 °C and replace/open fresh vial around 4 weeks.

Monitoring

No validated monitoring. In any human research, mood, suicidality, BP/heart rate, neurologic symptoms and standard safety labs would require formal protocol oversight.

Protocols vary widely between sources. Investigational compounds are not approved therapies, and approved products should follow their official labeling. Nothing here is medical advice.

Safety

Safety, side effects, and precautions

Side effects

Systematic human safety data are limited. Reported or plausible effects include headache, dizziness, fatigue, irritability, sleep changes, nausea and injection/nasal-site irritation depending on route.

Contraindications

No validated broad contraindication profile exists. Avoid unsupervised use in pregnancy/breastfeeding, severe psychiatric instability, seizure disorders or major neurologic disease unless the research/clinical protocol specifically addresses it.

Interactions

Formal interaction studies are limited. CNS-active medicines, sedatives, stimulants, antidepressants, anxiolytics and anticonvulsants may alter or obscure effects and should be reviewed clinically.

Stacks

Common stacks

No well-supported stack is highlighted for this peptide yet.

Questions

FAQ

References

Sources

Atlas

The Atlas verdict

PE-22-28 is scientifically interesting for TREK-1, depression models, but the current case is driven mainly by cell and animal data. Atlas would treat claimed benefits as hypotheses—not established human outcomes—and would put human safety, product quality, and controlled trials ahead of protocol optimization.

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