PE-22-28

Research-Grade

PE-22-28 comes from a line of research at a French CNRS institute on TREK-1, a background potassium channel in the brain. Mice lacking the TREK-1 gene showed more efficient serotonin neurotransmission, a smaller stress-hormone rise and resistance to depression in five behavioral models. The same group then identified spadin (PE 12-28), a 17-amino-acid peptide derived from the propeptide of sortilin (NTSR3), that blocks TREK-1, raised serotonin neuron firing and, after 4 days of treatment in mice, produced antidepressant-like effects with increased hippocampal CREB phosphorylation and neurogenesis. Because spadin's effect in mice lasted no more than about 7 hours, the researchers designed shorter analogs from its blood degradation products. PE-22-28, the seven C-terminal residues, blocked human TREK-1 channels in cells with an IC50 of 0.12 nM, compared with 40–60 nM for spadin. In mice it reduced immobility in the forced swim test after a single injection, shortened feeding latency in the novelty-suppressed feeding test after 4 days, increased hippocampal neurogenesis after 4 days, increased a synapse marker (PSD-95) in cultured neurons, and was active in a corticosterone-induced depression model; effects of PE-22-28 and its analogs lasted up to 23 hours. All of this comes from rodents and cells, largely from one laboratory. No human studies have been published, and PE-22-28 is not approved as a medicine.