Cognitive & Neuroprotective

PE 22-28

Also known as: Spadin fragment

Molecular Identifiers

Molecular Formula

C35H55N11O9

CAS Number

1801959-12-5

PubChem CID

165437303

Molecular Weight

773.89 Da

Overview

Neurogenic peptide derived from a spadin fragment. Inhibits the TREK-1 potassium channel, promoting neurogenesis and antidepressant-like effects. Promising research in depression models and neural plasticity.

Interest in PE 22-28 centers on the hypothesis of a fast-acting antidepressant via TREK-1 potassium channel inhibition — a target distinct from classical serotonergic antidepressants. In preclinical models, hippocampal neurogenesis and improved synaptic plasticity are observed within days rather than the weeks typical of SSRIs.

It is strictly an investigational peptide. It has no regulatory approval from any agency and no established clinical indication. When available, it circulates through research channels and compounding pharmacies as experimental use, in short 2-4 week subcutaneous protocols, with no consensus on optimal human dose or duration.

It was characterized as an active fragment derived from spadin (the sortilin propeptide), seeking a smaller, more stable form acting on the same target family. Human data remain very limited.

Among peptide nootropics, PE 22-28 is the only one with a direct affective target (antidepressant via TREK-1), distinct from the anxiolytic axis of Selank (GABAergic) and the pro-cognitive axis of Semax, Cerebrolysin, Dihexa (HGF/c-Met), and P21 (BDNF + anti-tau). It shares with the latter an advanced preclinical status without regulatory approval, and is also the least clinically mature of the group — no consolidated human registration and no dose consensus — in contrast with Selank/Semax (registered in Russia) and Cerebrolysin (approved in more than 40 countries).

Sequence (1 letter): GVSWGLR
Extended notation: Gly-Val-Ser-Trp-Gly-Leu-Arg

Peptide fragment — heptapeptide derived from spadin (positions 22-28 of the sortilin propeptide)

Half-life

~2-4 hours

Administration Route

Subcutaneous

Category

Cognitive & Neuroprotective

Mechanism of Action

  • TREK-1 potassium channel inhibition
  • Promotion of hippocampal neurogenesis
  • Antidepressant-like effects in preclinical models
  • Improvement of synaptic plasticity
  • Modulation of serotonergic signaling

Reported Side Effects

Adverse effects described in the literature. Severity and frequency vary between individuals.

  • Mild headache
  • Transient dizziness
  • Injection site pain

Product Properties

Purity >95%
Appearance White lyophilized powder
Solubility Soluble in water and bacteriostatic water
Source Solid-phase peptide synthesis (SPPS)
Storage Lyophilized: -20°C for up to 2 years, 2-8°C for up to 6 months. Reconstituted: 2-8°C for up to 4 weeks. Protect from light and moisture. Avoid repeated freeze-thaw cycles.

Presentations & Preparation

Vials of PE 22-28 found in the research market:

5 mg10 mg15 mg20 mg

Reconstitution

  • Diluent: Bacteriostatic water
  • Volume: 2 ml per vial
  • Slowly inject the diluent against the vial wall
  • Gently swirl until fully dissolved
  • Never shake

Storage

  • Lyophilized: Refrigerated 2-8°C
  • Reconstituted: Refrigerated 2-8°C (up to 30 days)
  • Protect from direct light
  • Do not freeze after reconstitution
Reconstitution Calculator

Scientific Studies

Published studies on PE 22-28.

2017 · Front Pharmacol

Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity

Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M

Related Peptides

Adamax

100-500 mcg via intranasal or subcutaneous · 1-2 times daily

Cerebrolysin

5-30 ml per injection · Once daily

Cortagen

Dihexa

DSIP

100-300 mcg per subcutaneous injection · Once daily

Epithalon

1-5 mg per subcutaneous injection (some protocols use 5-10 mg per full cycle) · Once daily or every other day