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Cognitive & Neurological

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

Clinical Trial

12 articles sourced

Knowledge Graph

(13 connections)
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Compound (Center)
Research Goal
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Research Evidence

(12)

Oxandrolone: Evidence-Based Research Review

6 min

Oxandrolone (17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one) is a synthetic oral anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Characterized by a unique substitution of an oxygen atom for the carbon at the C-2 position in the A-ring, oxandrolone exhibits a high anabolic-

Clinical Trial

Nandrolone Decanoate: Evidence-Based Research Review

6 min

Nandrolone decanoate (ND) is a long-acting injectable ester of the anabolic-androgenic steroid (AAS) nandrolone (19-nortestosterone). Characterized by a high anabolic-to-androgenic ratio, ND has been utilized clinically for decades to treat conditions involving protein catabolism, bone density loss,

Clinical Trial

Testosterone Enanthate: Evidence-Based Research Review

6 min

Testosterone enanthate (TE) is a long-acting esterified formulation of the primary endogenous androgen, testosterone. Since its clinical introduction in the 1950s, it has served as a cornerstone for testosterone replacement therapy (TRT) in male hypogonadism and a reference compound in clinical rese

Clinical Trial

Stanozolol: Evidence-Based Research Review

5 min

Stanozolol is a synthetic anabolic-androgenic steroid (AAS) derived from dihydrotestosterone (DHT). Characterized by a high anabolic-to-androgenic ratio, it is clinically distinguished by its pyrazole ring modification and 17α-alkylation. Originally developed for the treatment of hereditary angioede

Clinical Trial

GLP-1 Receptor Agonism in Metabolic Signaling

8 min

Survey of GLP-1, GIP, and glucagon receptor research for metabolic signaling and incretin physiology.

Clinical Trial

BPC-157 and Tissue Repair Signaling Pathways

9 min

Comprehensive review of BPC-157 mechanisms in tissue repair, angiogenesis, and mucosal healing.

Clinical Trial

BDNF Upregulation and Synaptic Plasticity Research

8 min

Investigation of BDNF-promoting peptides and their mechanisms in neurotrophin signaling.

Clinical Trial

Melanocortin Receptor Agonists and Neuroendocrine Signaling

8 min

Examination of melanocortin receptor signaling and synthetic agonist research applications.

Clinical Trial

Testolone (RAD-140): Evidence-Based Research Review

5 min

Testolone (RAD-140) is a potent, non-steroidal selective androgen receptor modulator (SARM) originally developed by Radius Health, Inc. It was designed to overcome the limitations of conventional androgen therapy, such as prostate enlargement and virilization, by exhibiting high tissue selectivity.

Preclinical

Trenbolone Acetate: Evidence-Based Research Review

6 min

Trenbolone acetate (TBA) is a potent synthetic 19-nortestosterone derivative classified as an anabolic-androgenic steroid (AAS). Originally developed for veterinary applications—specifically to increase muscle mass and feed efficiency in beef cattle—TBA has become a focal point of pharmacological in

Preclinical

Pinealon (Glu-Asp-Pro): Peptide Bioregulation of Neural Gene Expression and Neuroprotection

5 min

Pinealon is a tripeptide (Glu-Asp-Pro) bioregulator investigated for neuroprotective and cognition-supporting effects. This review summarizes in vivo evidence from animal models.

Preclinical

Adalank and the Selank Peptide Class: Anxiolytic Peptide Pharmacology and Translational Rationale

6 min

Adalank is a synthetic analog of the anxiolytic peptide Selank incorporating an adamantane moiety. This review outlines the pharmacological rationale and preclinical evidence from the Selank peptide class that informs its development.

Preclinical

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.

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.

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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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