PE-22-28
Spadin Analog PE-22-28
Overview
PE-22-28 is a synthetic analog of spadin — a peptide derived from the propeptide of TREK-1 potassium channels — that has demonstrated rapid antidepressant effects in animal models. It is notable for producing antidepressant effects within 24 hours in mouse models compared to the 2-4 week onset required for conventional antidepressants. PE-22-28 represents a novel mechanism for antidepressant action through TREK-1 channel blockade and is an emerging area of peptide psychiatry research.
Mechanism of Action
PE-22-28 works by blocking TREK-1 — a two-pore domain potassium channel expressed in serotonergic neurons of the dorsal raphe nucleus. TREK-1 channel activity normally hyperpolarizes serotonergic neurons reducing their firing rate and serotonin release. By blocking TREK-1 PE-22-28 depolarizes serotonergic neurons increasing their firing rate and serotonin release in projection areas including the hippocampus and prefrontal cortex — brain regions critical for mood regulation. This mechanism is distinct from SSRIs which block serotonin reuptake rather than increasing its release. The rapid onset (24 hours vs 2-4 weeks for SSRIs) is attributed to the immediate neurophysiological effect of increased serotonergic firing compared to the delayed synaptic adaptations required for SSRI efficacy.
Dosage Information
Typical Dose
Research compound — no established human dosing
Frequency
N/A
Administration
Intranasal in animal studies
Notes
Currently preclinical research compound. No human clinical trials completed. Significant interest as a rapid-acting antidepressant candidate.
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Evidence Score
0.07
Potential Side Effects
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Quick Facts
- Administration
- Intranasal in animal studies
- Typical Dose
- Research compound — no established human dosing
- Frequency
- N/A
- References
- 0 curated + 0 from PubMed
- Evidence Score
- 0.1 / 100