PE-22-28 Reconstitution Calculator

PE-22-28 is a 7-amino-acid peptide produced by shortening spadin, itself a fragment of the sortilin propeptide (PE),. It blocks the TREK-1 (K2P2.1) two-pore potassium channel, the depression target identified through sortilin/TREK-1 interaction studies,. In patch-clamp on hTREK-1/HEK cells, PE-22-28 inhibited TREK-1 with an IC50 of 0.12 nM versus 40–60 nM for spadin (in-vitro). In mice it reduced immobility in the forced-swim test, shortened latency to feed in novelty-suppressed feeding, and induced hippocampal neurogenesis after only 4 days (animal). TREK-1 blockade depolarizes neurons, raises 5-HT neuron firing, and drives CREB phosphorylation, BDNF expression, and synaptogenesis (PSD-95, synapsin),.

No. PE-22-28 has no regulatory approval in any jurisdiction, and no human clinical trials of the peptide exist. Human data are limited to serum measurements of the parent sortilin propeptide (e.g., levels rising after ECT in treatment-resistant depressed responders (observational)). PE-22-28 remains a preclinical research peptide.

All efficacy data come from parenteral injection: intraperitoneal delivery of mini-spadin in mice and intravenous delivery of spadin. No oral data exist; as a short unstructured peptide, gut degradation would be expected to render oral dosing ineffective (mechanistic). Community use is primarily subcutaneous, with intranasal as an alternative (community protocol). Once-daily dosing is consistent with the ~23 h pharmacodynamic window measured in vivo (animal).

No human dose is established. In mice, mini-spadin was given at 0.03 μg/kg i.p. in a low-dose neuroprotective phase and 3 μg/kg i.p. in the antidepressant phase; action is biphasic: low doses activated TREK-1 while higher doses inhibited it. Community protocols most commonly use 200–500 mcg subcutaneously once daily, or 100–200 mcg twice daily intranasally (community protocol). Given the sub-nanomolar IC50, start at the low end; very low doses may fall into the channel-activating range instead of blocking it.

The spadin class is rapid-onset: antidepressant effects appear within 4 days versus 3–4 weeks for fluoxetine,, and TREK-1 blockers reversed stress-induced depressive behavior at least 1 week before fluoxetine in rats. A single PE-22-28 dose retains activity up to ~23 h, versus ~7 h for spadin (animal). Neurogenesis and synaptogenesis markers increase after ~4 days of treatment,.

PE-22-28 is a tighter, longer-lived spadin: ~400-fold higher TREK-1 affinity (0.12 nM vs 40–60 nM IC50) and ~3× longer duration of action (23 h vs 7 h) (in-vitro/animal). N- or C-terminal modifications of PE-22-28 preserved or abolished channel block without changing binding, making it a modifiable scaffold for further analogs. Versus fluoxetine: both restore impaired hippocampal neurogenesis with chronic administration, but TREK-1 blockers act at least 1 week faster in the CUMS model.

No human safety data exist; use during pregnancy and lactation is contraindicated by default. In rodents, 3-week spadin treatment did not block cardiac IKr or IKs currents, alter systolic pressure or heart rate, or modify seizure thresholds, glycemia, or ischemic infarct size (animal). However, later rodent studies found that spadin increased acute flinching, secondary mechanical allodynia, and hyperalgesia, and produced tactile allodynia in naïve rats, indicating potential pro-nociceptive effects of TREK-1 blockade. PE-22-28 itself lacks equivalent dedicated toxicology. Report any adverse effects to your clinician; long-term human risk is unknown.

Published treatment windows in rodents run up to 3–4 weeks with sustained efficacy,. Community practice typically uses 4–6 week cycles followed by ≥2–4 weeks off, given the neuroplasticity-based mechanism (community protocol). Storage: no stability literature exists; standard peptide handling is lyophilized powder at −20 °C, then reconstituted in bacteriostatic water, refrigerated, and used within ~30 days (community protocol). PE-22-28 is not a scheduled controlled substance, but research-peptide legality varies by jurisdiction, verify before travel (community protocol).