PE-22-28

Preclinical only Neuroprotection 2 sources

PE-22-28 is a synthetic heptapeptide derived from spadin, a naturally occurring peptide fragment. It acts as a highly selective inhibitor of the TREK-1 potassium channel, demonstrating potent antidepressant-like and neuroprotective effects in preclinical models with a longer duration of action than its parent compound.

01Dosing reference

Amount

200-600 mcg/day (anecdotal/research)

Frequency

Once daily

Cycle

4-8 weeks on, followed by a break

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

TREK-1 Channel Inhibition

PE-22-28 selectively binds to and blocks the TREK-1 (K2P2.1) two-pore domain potassium channel in the brain.

Neuronal Excitability Modulation

By inhibiting this potassium channel, it alters the resting membrane potential, enhancing neuronal excitability and firing patterns.

Neurogenesis and Mood Regulation

This increased neuronal activity promotes neurogenesis (particularly in the hippocampus) and produces antidepressant-like effects without the overstimulation seen with some other agents.

03Human evidence

No published human clinical trials currently exist for PE-22-28.

While anecdotal reports exist in nootropic communities, formal human safety and efficacy data are lacking, and the compound remains strictly experimental.

04Preclinical evidence

PE-22-28 demonstrated potent antidepressant-like effects in animal models with a significantly longer duration of action than spadin.

In mouse models of depression, PE-22-28 showed efficacy up to 23 hours post-administration, compared to only 7 hours for spadin, while requiring a much lower dose.

The peptide showed high selectivity for TREK-1 without affecting hERG channels.

In vitro electrophysiological studies confirmed that PE-22-28 does not modify hERG channel activity, suggesting a favorable cardiac safety profile for potential future pharmaceutical development.

05What is known vs. unknown

Reasonably established

PE-22-28 is a 7-amino acid synthetic peptide derived from spadin.
It functions as a highly potent and selective inhibitor of the TREK-1 potassium channel.
In animal models, it exhibits a longer half-life and duration of action (up to 23 hours) compared to its parent compound.
Preclinical data suggests it promotes neurogenesis and exerts antidepressant-like effects.

Unknowns & limits

There are no published human clinical trials confirming its safety, efficacy, or optimal dosing in humans.
Long-term effects of sustained TREK-1 inhibition on brain function and overall health remain unknown.
The exact mechanisms by which TREK-1 inhibition translates to neurogenesis are still being elucidated.

06Safety & regulatory context

Regulatory statusPE-22-28 is an experimental research chemical and is not approved by the FDA or any other regulatory body for human use. It is currently available only for laboratory and preclinical research. While animal studies suggest a favorable safety profile—notably lacking hERG channel interference which is a common cardiac liability—human safety data is entirely absent. Potential side effects in humans are unknown, and its use outside of controlled research settings carries significant risks.

07Compared with Spadin

PE-22-28 vs. Spadin

Key difference

PE-22-28 is a shortened, synthetic analog of spadin that exhibits a much longer duration of action (up to 23 hours vs. 7 hours) and requires a significantly lower dose to achieve similar TREK-1 inhibition.

When researchers discuss each

Spadin is discussed as the naturally occurring endogenous peptide that first highlighted the TREK-1 channel as a therapeutic target, whereas PE-22-28 is discussed as the optimized, synthetic lead compound for potential drug development.

08Glossary

TREK-1

A two-pore domain background potassium channel found in the central nervous system that plays a role in regulating resting membrane potential and neuronal excitability.

Spadin

A naturally occurring peptide derived from the propeptide of sortilin that acts as an endogenous inhibitor of the TREK-1 channel.

Neurogenesis

The process by which new neurons are formed in the brain, often associated with learning, memory, and recovery from depression.

09Knowledge check

Q1What is the primary mechanism of action of PE-22-28?

Q2How does PE-22-28 compare to its parent compound, spadin, in preclinical studies?

Q3Which documented limitation in the dossier most directly prevents drawing conclusions about PE-22-28’s safety and efficacy in people?

Q4In the dossier’s stated comparison context, what role is spadin described as playing relative to PE-22-28?

Q5Which statement best matches the dossier’s safety and regulatory context for PE-22-28?

10Sources

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4 mg/day

Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.