PE-22-28
Spadin-derived peptide blocking TREK-1 channels. Studied for neuroplasticity and mood research.
Mechanism of Action
Bioregulator compound with targeted biochemical activity.
Evidence Chain
PE-22-28
COMPOUND
1 Research Goal
• Cognitive & Neurological
Evidence Strength
12 articles sourced
Knowledge Graph
(13 connections)Research Goals
(1)Research Evidence
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Overview
PE-22-28 is a synthetic peptide derived from spadin, a natural peptide that is a cleavage product of the somatostatin receptor 3 (SSTR3). PE-22-28 was developed as a research tool to study the effects of TREK-1 (TWIK-related potassium channel-1) channel blockade on neuroplasticity and mood regulation. TREK-1 channels are two-pore domain potassium channels that, when blocked, promote neuronal activity and neuroplasticity.
Mechanism of Action
PE-22-28 acts as a blocker of TREK-1 potassium channels. TREK-1 channels are background potassium channels that regulate neuronal resting membrane potential and excitability. By blocking TREK-1, PE-22-28 increases neuronal excitability and promotes neuroplasticity, including enhanced long-term potentiation (LTP) — a key mechanism of learning and memory. The TREK-1 blockade also influences serotonin neurotransmission and BDNF expression, connecting it to mood regulation and antidepressant mechanisms. This pathway is distinct from traditional monoamine-based antidepressant mechanisms.
Research Highlights
Animal studies have demonstrated PE-22-28's efficacy in producing antidepressant-like effects, with rapid onset compared to traditional antidepressants. Research showed improvements in learning and memory in behavioral models. Studies demonstrated enhanced neuroplasticity and increased BDNF expression following PE-22-28 administration. The rapid-acting antidepressant profile has generated interest in TREK-1 as a novel target for mood disorder research. Studies have also explored its potential in cognitive enhancement and neurodegenerative conditions.
Dosage & Administration
In research, PE-22-28 has been administered via subcutaneous and intranasal routes in animal models. No standardized human dosing protocols exist. For research use only (RUO).
Safety Profile
Preclinical studies have reported favorable safety profiles in animal models. However, long-term safety data in humans is absent. As an investigational peptide, full safety characterization is pending. Not approved by the FDA for any indication.
References
Mazella J, et al. Spadin and TREK-1. Sci Signal. 2010. Bhatt S, et al. PE-22-28 and antidepressant effects. Psychopharmacology. 2018. Moha Ou Maati L, et al. TREK-1 and depression. Neuropharmacology. 2012. All content is for educational and research purposes only.
Related Compounds
Synergy & Compatibility
(5)Computational assessment of bio-regulatory compatibility with compounds sharing research goals. Scores reflect half-life alignment, receptor target overlap, and bioavailability data.
Computational assessment based on available pharmacology data. Does not account for individual variability, dose-dependent effects, or unstudied interactions. For research use only.
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