Also known as: Spadin Analog, Sortilin-derived peptide
Half-life: Hours; precise value species-dependent
Last reviewed: · Published:
PE22-28 is a seven-amino-acid peptide analog of Spadin, a naturally occurring peptide derived from the sortilin neurotrophin receptor that selectively inhibits the TREK-1 potassium channel. TREK-1 is a two-pore-domain potassium channel expressed prominently in serotonergic neurons of the dorsal raphe nucleus; its activation is associated with reduced serotonergic firing and depression-like behavior. Knockout of TREK-1 in mice produces a depression-resistant phenotype, validating the channel as a therapeutic target for antidepressant drug development.
Spadin and its analogs (including PE22-28) act as selective TREK-1 blockers and produce robust antidepressant-like effects in mouse behavioral models (forced swim test, novelty-suppressed feeding) within hours of administration — substantially faster than the weeks-long onset of conventional SSRIs. PE22-28 was specifically optimized for stability and potency relative to native Spadin, retaining the antidepressant activity while being amenable to standard peptide synthesis and chronic administration.
PE22-28 has not been clinically tested in humans. It is sold by research-peptide vendors and used in subjective self-experimentation by users seeking rapid-onset mood effects, but the human safety and efficacy data are essentially absent. The TREK-1 inhibition mechanism is interesting and theoretically promising, but extrapolating from rodent forced-swim assays to human clinical depression is well-known to be unreliable.
Spadin was characterized by Marc Borsotto's group at the Institut de Pharmacologie Moléculaire et Cellulaire in France in 2010, building on the discovery that TREK-1 knockout mice were resistant to depression-like behavior. PE22-28 was developed as a more stable analog optimized for chronic use. Despite a decade of preclinical work demonstrating antidepressant activity in mouse models, the compound has not advanced to human clinical trials, and its presence on the research-chemical market substantially predates any clinical validation.
Animal tolerability studies of PE22-28 have reported good safety profiles, with no major adverse events at therapeutic doses. Human safety data is absent. TREK-1 is expressed outside the brain (notably in the heart and immune system) and chronic systemic inhibition may have effects that the brief rodent antidepressant assays don't capture. Self-experimentation outside a research protocol carries unquantified risks, particularly for users with cardiovascular conditions or on antidepressant medications.
Dose Range
100-500 mcg/kg
Frequency
Daily SubQ or IP
Duration
Per protocol
Dose Range
50-200 mcg
Frequency
Once or twice daily
Duration
2-4 weeks per cycle
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
5 mg
Water Type
Bacteriostatic water (BAC water)
Mixing Volume
2 mL
Half-Life
Hours; precise value species-dependent
Molecular Weight
~830 Da
Store reconstituted vial refrigerated at 2-8°C. Use within 14-21 days. Subcutaneous or intranasal administration; intranasal may offer better CNS bioavailability.
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FDA Status
Not FDA approved.
Legal Status
Unregulated research chemical.
USA
Not approvedResearch-only
EU
Not approvedNot authorized as medicinal product
UK
Not approvedClassified as research chemical
Australia
Not approvedTGA has not evaluated
Canada
Not approvedNot authorized for human use
Mazella J, Pétrault O, Lucas G, Deval E, Béraud-Dufour S, Gandin C, El-Yacoubi M, Widmann C, Guyon A, Chevet E, Taouji S, Conductier G, Corinus A, Coppola T, Gobbi G, Nahon JL, Heurteaux C, Borsotto M
PLOS Biology (2010)
Original characterization of Spadin demonstrating selective TREK-1 inhibition and fast-onset antidepressant activity in mouse behavioral models, establishing the pharmacological rationale for analogs like PE22-28.
View Study →Veyssière J, Moha ou Maati H, Mazella J, Gaudriault G, Moreno S, Heurteaux C, Borsotto M
European Journal of Pharmacology (2015)
Describes the optimization process by which shorter, more stable Spadin analogs (including the PE22-28 series) were developed, retaining antidepressant activity while improving drug-like properties.
View Study →Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thümmler S, Peng XD, Noble F, Blondeau N, Widmann C, Borsotto M, Gobbi G, Vaugeois JM, Debonnel G, Lazdunski M
Nature Neuroscience (2006)
Genetic validation of TREK-1 as an antidepressant target, demonstrating that mice lacking the channel show resistance to behavioral despair in standard depression assays.
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