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AICAR vs PE-22-28

Side-by-side comparison of key properties, dosing, and research.

Anti-Aging & LongevityFat Loss & Metabolic
AICAR
Cognitive Enhancement
PE-22-28
Summary
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.
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.
Half-Life
~2–3 hours
Relatively short; CNS effects may persist due to neurogenic mechanisms
Admin Route
SubQ, IV
SubQ, Intranasal
Research
Typical Dose
25–50 mg
200–400 mcg
Frequency
3–5 times per week
Once daily
Key Benefits
  • 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
  • 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
Side Effects
  • Hypoglycemia risk
  • Lactic acidosis at high doses (animal data)
  • Injection site irritation
  • Generally well tolerated in animal models
  • Limited human data available
  • Possible mild headache or transient mood changes at initiation
  • Injection site reactions (SC)
Stacks With