Tesofensine
Triple Monoamine Reuptake Inhibitor | Weight Reduction
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What is Tesofensine?
Tesofensine is a small-molecule compound, not a peptide, originally studied for Parkinson's and Alzheimer's research before its metabolic-research profile emerged in later trials. It works by blocking the reuptake of three brain chemicals — dopamine, norepinephrine, and serotonin — and researchers study it for metabolic and weight-management research. It is not FDA-approved and is not a substitute for an approved medication; research-grade tesofensine sold here is intended strictly for laboratory study, not for use in people or animals.
Key terms:
Tesofensine is a small molecule.
Tesofensine (NS2330) is a triple monoamine reuptake inhibitor: it blocks the reuptake of dopamine, norepinephrine, and serotonin, so more of each stays in circulation. It was originally developed for Parkinson's and Alzheimer's disease. Early trials reported significant weight reduction, which redirected it toward obesity research. In Phase 2 and Phase 3 trials, participants averaged 10-12% weight reduction over 24 weeks, among the largest figures reported for an investigational compound of this kind. Researchers attribute the effect to reduced appetite and higher energy expenditure, both driven through the central nervous system.
Key research areas
- Potent appetite suppression with significant weight reduction (9-12% over 24 weeks)
- Once-daily oral dosing with long half-life (~9 days)
- May also increase resting energy expenditure
- Different mechanism than GLP-1 agonists offers alternative approach
Researched dosing
This table reflects how researchers structured tesofensine study dosing in published trials — titration schedules and dose ranges presented as research methodology, not personal usage guidance.
| Phase | Dose | Frequency | Route |
|---|---|---|---|
| Weight-reduction studies — standard | 0.5mg | Once daily in the morning | Oral |
| Starting dose | 0.25mg | Once daily in the morning | Oral |
| Highest dose studied | 1.0mg | Once daily (higher side effect rate) | Oral |
Commonly cycled 24 weeks on, 0+ weeks off.
How it works
At the cell level, tesofensine research looks at how the compound blocks reuptake of three brain chemicals — dopamine, norepinephrine, and serotonin — raising their levels in brain regions involved in appetite and satiety signaling.
Tesofensine is a triple monoamine reuptake inhibitor that blocks reuptake of dopamine (IC50: 6.5nM), norepinephrine (IC50: 1.7nM), and serotonin (IC50: 11nM). This increases neurotransmitter levels in the hypothalamus and other brain regions controlling appetite and satiety. Recent research shows it silences GABAergic neurons in the lateral hypothalamus that normally promote feeding behavior.
Pharmacokinetics
- Peak
- 8 hr
- Half-life
- 220.8 hrs
- Cleared
- ~1099.2 hrs
Phase 2/3 Clinical Trials
Research applications
This section lists the research areas — metabolic and weight-management research chief among them — that scientists have studied for tesofensine in clinical trials; tesofensine is not FDA-approved and is not a substitute for an approved medication.
Weight Reduction
Phase 2/3 trials demonstrate 9-12% body weight reduction over 24 weeks, among the highest for investigational obesity drugs. Reduces hunger signals and increases satiety through central nervous system monoamine modulation. Clinical trials showed improvements in triglycerides, VLDL cholesterol, and insulin levels. Phase 3 data showed significant reduction in visceral fat, the metabolically harmful fat around organs.
Metabolic
Clinical trials demonstrated improvements in triglycerides, VLDL cholesterol, insulin levels, and significant reductions in visceral fat.
Dosage reference
- Doses used in research
- 0.25–0.5 mg
- Frequency in studies
- Once daily, morning preferred
- Handling
- Reconstituted solution — research use only; not for administration
- Timeline reported in studies
- Appetite reduction: Days 1-7, Weight Reduction: Weeks 2-4 onward, Full effects: 12-24 weeks
- Storage
- Room temperature, protect from moisture
- Cycle length
- 12-24 weeks typical in clinical trials
- Break between cycles
- Unknown - long half-life means effects persist weeks after stopping
Interactions
This list shows which other compounds researchers flag as needing caution alongside tesofensine, largely because of its effect on the same brain-chemical pathways as several psychiatric medications.
Reconstitution & storage
This section covers how research-grade tesofensine capsules are handled and stored — since it's studied as an oral compound rather than an injectable, the notes differ from peptide reconstitution.
- Due to long half-life (~9 days), steady state reached after several weeks
- Do not take in the evening due to potential insomnia
- Store the reconstituted solution refrigerated (2–8°C), labeled with the date and concentration, for laboratory research use only.
Lyophilized: Room temperature, use within As per manufacturer
Reconstituted: 2-6°C, use within N/A - oral capsule
Quality indicators
This section lists what researchers check to confirm a tesofensine sample's identity and purity, since it is only available through compounding sources rather than an FDA-approved manufacturer.
Not FDA Approved - Tesofensine is investigational and not approved for obesity treatment in the US
Compounded Products - Currently only available through compounding pharmacies - quality varies
Third-Party Testing - Verify purity through independent certificate of analysis (COA)
Proper Dosing - Capsules should be accurately dosed at 0.25mg or 0.5mg increments
Unknown Sources - Avoid products without verifiable testing or from unregulated sources
Combination Products - Be cautious of pre-mixed combinations without clinical safety data
What to expect
This timeline reflects what the clinical-trial literature reports at each study stage — research context for comparing studies, not a personal-results promise.
Noticeable appetite reduction, possible dry mouth and mild insomnia
Initial weight reduction begins (1-2kg typical)
Significant weight reduction accumulates (5-8% body weight)
Continued weight reduction reaching 10-12% in responders
Safety notes
This section covers tesofensine's regulatory status and handling cautions — research-use-only scope and safety data drawn from the clinical literature, provided as reference context for laboratory researchers, not medical guidance.
- Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants
- Not recommended for those with cardiovascular disease or uncontrolled hypertension
- May cause insomnia - take in the morning only
- Psychiatric effects possible - avoid with depression/anxiety history
- Long half-life means side effects persist if they occur
- Regular cardiovascular monitoring recommended
- May increase heart rate by 5-8 bpm (dose-dependent)
- Can modestly increase blood pressure (1-3 mmHg typical)
- NOT FDA approved - investigational compound only
Regulatory status
- Not approved by the FDA for any indication.
- Supplied and described for laboratory research use only — not for human or veterinary use.
Community data
Community Insights
Based on data the community reported. Not clinical proof.
References
Landmark randomized, double-blind, placebo-controlled trial demonstrating dose-dependent weight reduction. The 0.5mg dose showed 9.2% weight reduction, approximately double that of FDA-approved obesity medications at the time. Up to 10.6% weight reduction with 203 participants.
Open-label extension study showing sustained weight reduction over 48 weeks of treatment, with participants maintaining 13-14kg weight reduction.
Phase 3 registration trial meeting primary and secondary endpoints. Demonstrated significant reductions in waist circumference, body fat, visceral fat, triglycerides, and insulin levels.