PE-22-28

Cognitive Research compound (not approved for human use)

Spadin-derived peptide (TREK-1 channel blocker) · also known as PE 22-28, Spadin analog

For reference only — not medical advice. Figures are commonly reported values compiled from published sources and may be wrong or out of date. Many compounds listed are not approved for human use. Talk to a licensed clinician before using any compound.

PE-22-28 is a shortened analog of spadin, a natural peptide released from the sortilin receptor propeptide. It was engineered to keep spadin's block of the TREK-1 potassium channel while being more stable in the body. Everything known about it comes from laboratory and animal studies.

Commonly reported dosing (10 mg vial)

Reconstituted with 3 mL → 3.333 mg/mL.

Phase	Dose	Volume	U-100 units
Starting Below about 2 units on a U-100 syringe at this concentration; not reliably measurable.	50 mcg	0.015 mL	1.5
Standard	100 mcg	0.03 mL	3
Higher	200 mcg	0.06 mL	6

Frequency: Once daily, subcutaneous · Half-life: Not well characterized in humans

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Commonly reported reconstitution steps

Vials are usually brought to room temperature (about 15-20 minutes) first.
3 mL of bacteriostatic water is added slowly down the inside wall of the 10 mg vial.
The vial is swirled gently until clear, not shaken.
This gives 3.33 mg/mL. Mixed vials are typically labeled with the date and refrigerated.

Storage

Before mixing: Lyophilized vials are commonly stored frozen (-20 °C).

After mixing: Reconstituted solution is commonly kept refrigerated (2-8 °C) and protected from light.

Commonly used within 28 days of mixing.

How it works

By inhibiting TREK-1 channels, PE-22-28 is thought to change neuronal excitability and serotonergic signaling in ways that mimic antidepressant responses seen in rodents.

Researched for

Studied in rodents for antidepressant-like behavior with faster onset than conventional agents.
Investigated as a more stable alternative to spadin in TREK-1 inhibition assays.

Notes

No human clinical trials are known; the dosing figures are community-reported and extrapolated.
Regimens in the reference are weight-independent micro-doses, which are small volumes on a U-100 syringe.