TREK-1 channel antagonist (nootropic peptide) · Also known as Spadin analog, Shortened spadin
A synthetic 7-amino-acid peptide derived from spadin, a naturally occurring fragment of the sortilin protein. It blocks the TREK-1 potassium channel with roughly 300 times greater potency than its parent peptide and promotes neurogenesis in the hippocampus.
PE-22-28 emerged from French neuroscience research published in 2017 that optimized the spadin peptide for better stability and receptor affinity. The TREK-1 channel was identified as a depression target after knockout mice lacking this channel showed resistance to depressive behavior. All current evidence comes from cell culture and rodent studies; no human trials have been conducted.
PE-22-28 selectively inhibits the TREK-1 two-pore potassium channel with an IC50 of 0.12 nM, compared to 40 to 60 nM for the parent peptide spadin. By blocking this channel, it increases neuronal excitability and modulates serotonergic neuron firing rates. The downstream effects include activation of CREB signaling pathways involved in learning, memory, and mood regulation.
In mouse studies, PE-22-28 significantly stimulated hippocampal neurogenesis and synaptogenesis after just four days of treatment at 3.0 to 4.0 mcg/kg/day. Its improved in vivo stability (action lasting up to 23 hours versus 7 hours for spadin) makes it a more practical research tool. Efficacy data comes from animal behavioral models like the forced swim test and novelty suppressed feeding test. No human pharmacokinetic or safety data exists.
No established human dose
N/ANo established human dose
N/AMost side effects tend to improve as your body adjusts.