PE-22-28 vs Tesofensine
Side-by-side comparison of key properties, dosing, and research.
Cognitive Enhancement
PE-22-28Fat Loss & Metabolic
Tesofensine- 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.
- Tesofensine is a triple monoamine reuptake inhibitor (TMRI) that blocks reuptake of serotonin, dopamine, and norepinephrine. Originally developed for Alzheimer's and Parkinson's disease, it was repurposed as a potent weight loss agent after clinical trials demonstrated substantial fat loss via appetite suppression and increased energy expenditure.
- Half-Life
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- 8-10 days (exceptionally long; accumulates over weeks)
- Admin Route
- SubQ, Intranasal
- Oral
- Research
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- Typical Dose
- 200–400 mcg
- 0.25-0.5 mg per day
- Frequency
- Once daily
- Once 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
- Potent appetite suppression via triple monoamine reuptake inhibition
- Significant weight loss (8-12% body weight in phase II trials at 0.5 mg)
- Increases basal metabolic rate and energy expenditure
- Reduces fat mass preferentially over lean mass
- Potential cognitive benefit via dopaminergic and noradrenergic enhancement
- Longer half-life than sibutramine allows once-daily dosing
- 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)
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- Stacks With
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