PE-22-28 vs AICAR
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.
- AICAR is a cell-permeable AMP analog that activates AMPK (AMP-activated protein kinase) — the master metabolic switch that triggers fat burning, mitochondrial biogenesis, and adaptations normally only achieved through exercise. It has been called the 'exercise in a pill' compound.
- Half-Life
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- ~2–3 hours
- Admin Route
- SubQ, Intranasal
- SubQ, IV
- Research
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- Typical Dose
- 200–400 mcg
- 25–50 mg
- Frequency
- Once daily
- 3–5 times per week
- 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
- AMPK activation mimics aerobic exercise adaptations
- Increased fat oxidation and endurance
- Mitochondrial biogenesis (PGC-1alpha)
- Improved insulin sensitivity and glucose metabolism
- Anti-inflammatory effects
- Potential cardiac protection during ischemia
- Synergistic with actual exercise training
- Reduces hepatic glucose production
- 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)
- Hypoglycemia risk
- Lactic acidosis at high doses (animal data)
- Injection site irritation
- Stacks With
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