PE-22-28 vs Exenatide
Side-by-side comparison of key properties, dosing, and research.
- Summary
- PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
- Exenatide is a GLP-1 receptor agonist derived from the Gila monster lizard peptide exendin-4, with 53% homology to human GLP-1 and natural resistance to DPP-4 degradation. Available as twice-daily (Byetta) or once-weekly (Bydureon) formulation, it is also being studied for Parkinson's disease neuroprotection.
- Half-Life
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- ~2.4 hours (Byetta/twice-daily); Bydureon BCISE: weekly via microsphere release
- Admin Route
- SubQ, Intranasal
- SubQ
- Research
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- Typical Dose
- 200–400 mcg
- 5 mcg, titrate to 10 mcg
- Frequency
- Once daily
- Twice daily
- Key Benefits
- Rapid-onset antidepressant effects (within 24 hours)
- Promotes hippocampal neurogenesis
- Improves cognitive performance and memory
- Reduces anxiety and depressive behavior
- Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
- May help treatment-resistant depression
- Neuroprotective effects
- Blood glucose control in type 2 diabetes
- Weight loss (average 2–3 kg in clinical trials)
- Once-weekly extended-release formulation available
- Reduces appetite and food intake
- Possible neuroprotective in Parkinson's disease (Phase II trials)
- Reduces systemic inflammation
- May protect pancreatic beta cells
- Cardiovascular neutral or potentially protective
- Side Effects
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
- Nausea (most common, especially initially)
- Vomiting
- Diarrhea
- Headache
- +4 more
- Stacks With
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