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PeptideGrey AreaPreclinical

PE-22-28

About

About PE-22-28

PE-22-28 is a synthetic peptide fragment of spadin, a peptide derived from the sortilin proprotein, which acts as an antidepressant through TREK-1 potassium channel blockade — a novel non-monoamine mechanism. Preclinical data shows rapid antidepressant effects comparable to ketamine without dissociative side effects. It is being investigated as a fast-acting antidepressant for treatment-resistant depression.

Science

Mechanism of Action

Selectively inhibits TREK-1 (TWIK-related potassium channel 1) in the raphe nuclei and hippocampus, increasing serotonergic neurotransmission and BDNF expression through a mechanism distinct from SSRIs and entirely independent of monoamine reuptake inhibition.

Dosing

Typical Protocol

Intranasal administration in animal studies; human dosing not yet established. Research stage only.

⚠ Protocol information is for educational purposes only. Dosing must be determined by a licensed physician based on individual health status and goals.

Regulatory

Legal Status in 2026

Grey Area

This compound occupies a regulatory grey area in 2026. It is neither explicitly FDA-approved nor clearly illegal for personal use, but it lacks formal clinical approval and may not be legally sold for human use in all contexts. Proceed with caution: source quality is variable, and regulatory status can change. Always consult a physician.

Evidence

Evidence Tier

Preclinical

Evidence primarily from animal studies, cell cultures, or small pilot human trials. Results are promising but have not yet been confirmed in large-scale human RCTs. Effects in humans may differ from animal models.

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