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also known as: Peptide E 22-28, Spadin analog, TRIP8b-derived antidepressant
Half-life: Unknown; estimated short
PE 22-28 is a synthetic 7-amino acid peptide fragment derived from the TREK-1 potassium channel blocker SPADIN, itself derived from the propeptide of neurotensin receptor 3. It acts as a rapid-onset antidepressant and cognitive enhancer in animal models, without the side effects of conventional antidepressants.
Mechanism of Action
Blocks TREK-1 (TRAAK-related potassium channel), increasing neuronal excitability in mood-regulating brain regions. Promotes BDNF expression and hippocampal neurogenesis. Acts on the same pathway as fluoxetine (Prozac) but more selectively via a different mechanism.
Mazella et al. (Science, 2010) first described spadin as an antidepressant acting on TREK-1. PE 22-28 is the more potent, more specific truncated analog with improved CNS penetration.
Semax raises BDNF via TrkB; PE 22-28 raises BDNF via TREK-1 blockade — complementary neurotrophin upregulation.
Selank provides anxiolysis; PE 22-28 provides antidepressant and cognitive effects — comprehensive mood/cognition stack.
Dihexa drives synapse formation; PE 22-28 promotes neurogenesis and mood — structural and functional neurological repair.
None listed.
PE 22-28 for daytime mood/cognition; DSIP for night-time sleep consolidation — full day/night mental health protocol.
Storage
Refrigerate at 2–8°C (36–46°F). Protect from light.
Reconstitution
Reconstitute with bacteriostatic water.