PE-22-28

PE-22-28 (Spadin-derived TREK-1 inhibitor)

Evidence & Status

  • Preliminary / Experimental
  • Preliminary

At a Glance

A short synthetic peptide derived from the neurotensin receptor propeptide, studied as a potential novel antidepressant through TREK-1 potassium channel inhibition — a mechanism entirely distinct from conventional antidepressant pharmacology. All available research has been conducted in rodent models.

Plain English

Researchers study PE-22-28 because it may work on a pathway implicated in depression that is entirely separate from the serotonin, dopamine, and norepinephrine systems targeted by conventional antidepressants. Scientists are interested in TREK-1 — a specific type of potassium channel in neurons — as a potential target for novel antidepressant approaches. Animal studies have shown rapid-onset antidepressant-like effects and evidence of hippocampal neurogenesis stimulation. No human trials have been conducted, and this remains a very early-stage area of research.

Overview

PE-22-28 is a seven-amino-acid shortened spadin analogue derived from sortilin/NTSR3 propeptide research. It has been studied as a TREK-1 inhibitor in cell and mouse models, including antidepressant-like behavioral, neurogenesis, and synaptogenesis findings. These are preclinical findings and do not establish antidepressant efficacy or safety in people.

Research Summary

The primary PE-22-28 publication describes a seven-amino-acid shortened spadin analogue with TREK-1 inhibition in hTREK-1/HEK cells and antidepressant-like, neurogenesis, and synaptogenesis findings in mouse models. These are preclinical findings and do not establish antidepressant efficacy or safety in people.

Research Areas

  • Depression and antidepressant mechanisms
  • TREK-1 potassium channel inhibition
  • Hippocampal neurogenesis
  • Neuroplasticity

Safety & Risks

Serious Risks

  • Unknown; no human safety data
  • TREK-1 channel modulation has wide physiologic effects
  • CNS target with incompletely characterized human pharmacology

Reported Side Effects

  • Not well-characterized in humans
  • No established human adverse-effect profile
United States
Research only
United Kingdom
Research only
Australia
Research only
Canada
Research only

Citations & Sources