PE-22-28
A synthetic derivative of Spadin that targets TREK-1 channels, potentially offering antidepressant effects and neurogenesis.
Common Dosage
Research phase (typically nasal)
Category
Nootropic
- Mood enhancement
- Cognitive support
- Neurogenesis
PE-22-28 is a synthetic derivative of Spadin, a naturally occurring peptide generated from proteolytic cleavage of prosaposin. Spadin was discovered by French researchers who identified it as an endogenous inhibitor of the TREK-1 two-pore potassium channel — a channel now recognized as a significant regulator of mood and depression. PE-22-28 was developed as an optimized fragment with enhanced bioavailability and TREK-1 inhibitory potency, representing an entirely novel mechanism for antidepressant intervention.
TREK-1 is a background potassium channel that, when overactivated, hyperpolarizes neurons and reduces serotonergic signaling. PE-22-28 inhibits TREK-1, effectively increasing neuronal excitability in mood-regulating circuits. In animal models, TREK-1 knockout mimics the effect of antidepressants, and PE-22-28 reproduces this effect pharmacologically. It also appears to promote hippocampal neurogenesis — a process associated with long-term antidepressant effects.
- Treatment-resistant depression research
- Hippocampal neurogenesis promotion
- Anxiety reduction
- Serotonergic system modulation without direct serotonin receptor binding
- Cognitive enhancement associated with neurogenic mechanisms
Antidepressant Effect in Rodent Models
PE-22-28 has demonstrated antidepressant effects in the forced swim test and learned helplessness models that are comparable to conventional antidepressants, but with onset within days rather than weeks — potentially attributable to its neurogenic rather than purely serotonergic mechanism.
- Human clinical data is entirely absent — this is a preclinical research compound
- TREK-1 inhibition across different tissue types (cardiac, neurological) carries off-target risk profiles not yet characterized
- Route of administration in humans is not established — nasal delivery protocols are anecdotal
- Individuals on antidepressants or serotonergic medications should not self-experiment without medical supervision
- Unknown (Research)