COMPOUND

Compounds / Cognitive

PE-22-28

PE 22-28 (synthetic 7-amino-acid spadin analog; mini-spadin)

Cognitive SubQ · Nasal Not FDA approved

Synthetic heptapeptide derivative of the naturally-occurring peptide spadin. Acts as a high-affinity TREK-1 potassium channel antagonist with antidepressant and neurogenic effects in preclinical models. NOT a Khavinson bioregulator. This is a French research-line peptide (Borsotto / Heurteaux lab, Sophia Antipolis). All efficacy data is animal-only; zero published human safety or PK data.

At a glance

Half-life
~23 h Action duration in mice ~23 hours (vs spadin ~7h). Plasma half-life specifically not characterized. Value reflects functional/behavioral duration. PMID 28955242.
Routes
SubQ · Nasal
Vial sizes
10 mg
Evidence base
1 study 1 preclinical

Mechanism

TREK-1 (TWIK-related K+ channel) inhibitor with IC50 ~0.12 nM. TREK-1 is a two-pore potassium channel; mice with TREK-1 deletion are resistant to depression. Blocking TREK-1 produces an antidepressant-like effect. Spadin is endogenously derived from sortilin processing; PE-22-28 extends spadin's action duration from ~7h to ~23h. Documented preclinical effects: antidepressant activity in forced swim test, novelty-suppressed feeding, learned helplessness; effective via IP, IV, and oral gavage; increased hippocampal neurogenesis (BrdU); increased PSD-95 expression (synaptogenesis marker).

Dosing

No standardized human dosing has been established. Every catalogued study for PE-22-28 is preclinical or a literature review. Amounts used in animal models do not translate directly to humans.

Published evidence

  1. Animal in vivo 2017

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

    Veyssiere J, Borsotto M, Heurteaux C, et al. ACS Chemical Biology

    PE-22-28 displayed superior TREK-1 inhibition (IC50 0.12 nM), 23h action duration, and antidepressant effects in mice via multiple routes (IP, IV, oral gavage).

    PMID 28955242

Reported side effects

No human safety data published
Unknown Mild · All AE data is from animal models only. No published human safety study.
Theoretical anxiogenic effect at high doses
Theoretical Mild · TREK-1 modulation effects in humans untested.

Interactions

  • SSRI class Caution

    Both target depressive pathways; TREK-1 antagonism is mechanistically distinct from SSRI but combined effect untested.

Reconstitution and storage

Lyophilized; reconstitute in BAC water. Intranasal formulations usually 0.1-0.5% solutions.

Lyophilized: room temp short-term. Reconstituted: refrigerate.

Open the reconstitution calculator for PE-22-28