PE-22-28

Overview

PE-22-28 is a synthetic peptide derived from the spadin family, designed to inhibit TREK-1 (TWIK-Related Potassium Channel 1). TREK-1 deletion in animal models produces an antidepressant-like phenotype, making TREK-1 inhibitors of interest for mood disorder research. PE-22-28 is a more potent and selective analog than the parent compound spadin.

Mechanism of Action

PE-22-28 blocks TREK-1 potassium channels, increasing neuronal excitability in mood-relevant brain regions. TREK-1 inhibition enhances serotonergic and noradrenergic neurotransmission and promotes hippocampal neurogenesis. The antidepressant effect occurs within days rather than the weeks required by traditional SSRIs, suggesting a different mechanistic pathway.

Research Context

Studies have shown rapid antidepressant-like effects in behavioral models, along with increased BDNF expression and hippocampal neurogenesis. The fast onset of action distinguishes it from conventional antidepressant mechanisms.

Key Research Areas

Considerations for Researchers

Limited vendor availability. Relatively new to the research market. Store lyophilized at -20C. Intranasal administration may be used for CNS delivery.