Tesofensine Research Overview (also known as NS 2330, Tesofensine HCl, Triple monoamine reuptake inhibitor)
A triple monoamine reuptake inhibitor originally developed for Parkinson's disease, studied for its effects on appetite suppression through dopamine, norepinephrine, and serotonin reuptake inhibition. Research has shown meaningful weight-loss effects in clinical trials.
What Is Tesofensine?
Tesofensine is a presynaptic triple monoamine reuptake inhibitor — blocking reuptake of dopamine, serotonin, and norepinephrine simultaneously — originally developed for Parkinson's disease before its profound weight-loss effects were discovered in clinical trials. It produces among the largest weight losses documented for any oral anti-obesity agent in Phase 2 trials.
Mechanism of Action
By inhibiting reuptake of dopamine, serotonin, and norepinephrine, Tesofensine increases the synaptic availability of all three monoamines simultaneously. The weight-loss effects are mediated primarily through central mechanisms: appetite suppression via hypothalamic monoamine signaling, activation of reward circuits in ways that reduce food-seeking behavior, and modulation of the melanocortin system that regulates energy balance.
Obesity Clinical Data
The TIPO Phase 2 trial demonstrated dose-dependent weight loss: 6.5% at 0.25mg, 11.3% at 0.5mg, and 12.8% at 1mg over 24 weeks — versus 2.2% placebo. These results rank among the most significant for any oral weight-loss agent. Phase 3 trials are underway with particular focus on cardiovascular safety, given the monoaminergic mechanism. Tesofensine's original Parkinson's indication reflected its dopaminergic reuptake inhibition, which contributes to its unique appetite-modulating profile.
Quick Reference
| Literature-Reported Dose Range | 0.25-0.5mg once daily |
| Literature-Reported Frequency | Once daily, morning |
| Literature-Reported Cycle Length | 12-24 weeks typical |
| Literature-Reported Washout | Effects persist weeks after stopping due to long half-life |
| Storage | Room temperature |
| Timing | Morning to avoid insomnia |
Research Indications
Weight Loss
Significant Weight Reduction
Phase 2/3 trials show 9-12% weight loss over 24 weeks, superior to many approved medications
Appetite Suppression
Potent central appetite suppression through triple monoamine mechanism
Metabolic Improvements
Improvements in triglycerides, insulin, and visceral fat in clinical trials
Metabolic
Increased Energy Expenditure
May boost resting metabolic rate through noradrenergic effects
Lipid Improvements
Reductions in VLDL cholesterol and triglycerides observed
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below) — not a personal dosing recommendation.
| Research Application | Dose | Frequency | Route |
|---|
| Weight Loss | 0.5mg | Once daily | Oral |
| Starting Dose | 0.25mg | Once daily | Oral |
Timing
Recommended administration window: morning to avoid insomnia. Typical onset: appetite reduction: 1 week, Weight loss: 2-4 weeks.
Peptide Interactions
High risk of serotonin syndrome due to overlapping serotonergic activity. Both increase serotonin levels which can lead to dangerous accumulation.
Risk of serotonin syndrome and excessive norepinephrine stimulation. Combination may cause severe hypertension and cardiac effects.
Absolutely contraindicated. Combination can cause life-threatening serotonin syndrome, hypertensive crisis, and death.
Overlapping dopaminergic and noradrenergic effects may cause severe cardiovascular stress, hypertension, and increased abuse potential.
Both affect dopamine and norepinephrine reuptake. Combination increases risk of seizures, hypertension, and cardiac effects.
No clinical data on combination. Different mechanisms (GLP-1 vs monoamine) but combined use is not recommended without medical supervision.
Metoprolol may counteract tesofensine-induced heart rate and blood pressure increases while preserving appetite suppression. Studied in preclinical models.
May enhance stimulant-like effects and cardiovascular stress. Consider reducing caffeine intake while using tesofensine.
Reported Research Timeline
01Week 1–2 (reported in cited studies): appetite suppression begins, possible initial side effects
02Week 2–4 (reported in cited studies): early weight loss (1-2kg)
03Month 1–3 (reported in cited studies): significant weight loss (5-8%)
04Month 3–6 (reported in cited studies): maximum effects (9-12% weight loss in responders)
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
NOT FDA approved - investigational compound
Not Recommended with MAOIs, SSRIs, SNRIs, and stimulants
May modestly increase heart rate and blood pressure
Not for those with cardiovascular disease or uncontrolled hypertension
Can cause insomnia - morning dosing only
Long half-life (~9 days) means prolonged effects and side effects
Regular cardiovascular monitoring recommended
Seek Medical Attention If:
Rapid or irregular heartbeat
Significant blood pressure elevation
Severe insomnia or psychiatric symptoms
Signs of serotonin syndrome
Chest pain or cardiovascular symptoms
Quality Indicators
Acceptable Range
Investigational Status
Not FDA approved - use under medical supervision only
Verified Marker
Third-Party Testing
Verify purity with certificate of analysis
Quality Concern
Unverified Sources
Avoid products without quality documentation
Research Citations
Research Focus
Weight loss, Appetite suppression, Dopamine/serotonin/norepinephrine reuptake inhibition, Obesity, Parkinson's research
Verified Vendors Carrying Tesofensine
Frequently Asked Questions
What should researchers watch for with Tesofensine?
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
What should researchers expect over time with Tesofensine?
Week 1–2 (reported in cited studies): appetite suppression begins, possible initial side effects
How is Tesofensine typically administered in research?
As reported in cited literature and research-community logs (see Research Citations below) — not a personal dosing recommendation.
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