Supplement Scholar
Nootropic / Mood

PE-22-28

Research compound. This is not a dietary supplement. Unless it is identified as an approved prescription drug, it is not approved by the FDA for human use. This page summarizes published research for education only; we do not sell it or link to sellers.

PE-22-28. Seven-amino-acid spadin analog that blocks the TREK-1 potassium channel; fast antidepressant-like effects in mice.

How it works. Inhibits TREK-1 potassium channels, raising neuron excitability in mood circuits and promoting neurogenesis.

What the research supports. 1 graded claims. Strongest: Rapid antidepressant-like effects in mice (preclinical).

Side effects and interactions. 1 medication interaction listed. No serious side effects listed at normal doses.

Common forms. Available as Intranasal or injection (research only).

Community. Experiences from people who have tried PE-22-28. Anecdotes are not medical advice.

PE-22-28. Seven-amino-acid spadin analog that blocks the TREK-1 potassium channel; fast antidepressant-like effects in mice.

7-residue chainC35H55N11O9 · 773.9 g/mol

What it is

Derived from spadin, a fragment of the sortilin propeptide. In rodents it produced antidepressant-like effects within days and increased new neuron growth in the hippocampus. No human trials.

Also called

Spadin analog

How it works

Inhibits TREK-1 potassium channels, raising neuron excitability in mood circuits and promoting neurogenesis.

Pathways

  • TREK-1 channel inhibition
  • Hippocampal neurogenesis
  • Serotonergic neuron firing

Effects

  • ↑Hippocampal neurogenesis (mice) increases
  • ~Mood-related neuron firing modulates

What the research supports

Rapid antidepressant-like effects in micepreclinical

Strong: consistent results across large trials or meta-analyses. Moderate: several trials, mostly positive. Limited: small or mixed studies. Preclinical: animal or cell research only.

Side effects & interactions

Common side effects

  • Unknown in humans

Medication interactions

Antidepressantsmoderate

Unstudied combination; effects on mood circuits could add up.

Check any supplement–medication combination with your pharmacist before starting.

Common forms

  • Intranasal or injection (research only)

Discussion

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