Tesofensine (NS2330)
Tesofensine is a triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for Parkinson's disease. Weight loss was discovered as a consistent side effect. Phase IIb (Lancet 2008, n=203) showed 9.2% weight loss at 0.5 mg over 24 weeks, about double any approved drug at the time. Heart rate elevation has limited its path to approval.
FormBlends Peptide Context
Reviewed May 14, 2026Treat Tesofensine peptide guide as context for a safer next conversation. It should help with frame benefits, dosing, evidence strength, sourcing, and safety boundaries in one place, while keeping the reader focused on peptide therapy, evidence limits, provider oversight, and the difference between general information and personal medical advice.
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Clinical decision snapshot
Tesofensine authority snapshot
Tesofensine is evaluated by mechanism, evidence quality, regulatory status, practical access, and safety questions a licensed clinician would need to review before use.
Evidence signal
Meaningful evidence with limits
Regulatory reality
Not a peptide; not affected by peptide compounding regulations
Safety screen
Dry mouth (most frequent), Nausea, constipation, diarrhea, Insomnia should be reviewed in context.
This page currently connects to 11 source-backed evidence items through visible references or structured citation data.
Decision path
What is the supervised-review path for Tesofensine?
Tesofensine should be evaluated by evidence quality, safety status, source quality, dosing context, and whether the goal fits a legitimate clinical pathway. This page is a research and decision aid, not a self-prescribing guide.
- Peptide
- Tesofensine
- Category
- Weight Loss
- Evidence
- Meaningful evidence with limits
- FDA status
- Not FDA approved
Step 1
Check evidence level
Tesofensine has solid Phase IIb data. Astrup et al. (Lancet 2008, PMID: 18950853) showed 9.2% weight loss at 0.5 mg over 24 weeks in 203 patients, about double any approved obesity drug at the time. Appel et al. (Eur Neuropsychopharmacol 2014, PMID: 24239329) confirmed dose-dependent DAT occupancy via PET imaging. Hansen et al. (Neuropsychopharmacology 2010, PMID: 20200509) identified the alpha-1/D1 appetite suppression pathway.
Review evidenceStep 2
Screen safety context
Dry mouth (most frequent), Nausea, constipation, diarrhea, Insomnia should be discussed in light of history, dose, and source.
Check side effectsStep 3
Confirm access route
If FormBlends offers access, review the product page and provider pathway before deciding.
Review product accessLast updated: April 6, 2026
Typical Dosage
Oral capsule, once daily in the morning. Starting: 0.25 mg/day for 1-2 weeks. Maintenance: 0.5 mg/day (most studied therapeutic dose). The 1.0 mg dose showed more weight loss but caused unacceptable cardiovascular effects and was dropped.
Administration
Oral capsule
Typical Cost
$90-300/month
FDA Status
Not FDA Approved
Half-Life
Approximately 220 hours (~9 days). Active metabolite M1 (NS2360): ~374 hours (~16 days). Effects persist for weeks after discontinuation.
Onset of Action
Tmax 6-8 hours. Appetite suppression typically within first few days. Steady state requires several weeks given the 9-day half-life. Full weight loss effects measured at 12-24 weeks.
Bioavailability
Over 90% oral bioavailability. Absorption not affected by food.
About Tesofensine
Tesofensine (NS2330) is a phenyltropane derivative with CAS number 195875-84-4 and molecular weight 328.28 Da. Molecular formula: C17H23Cl2NO. The origin story is interesting. NeuroSearch A/S (Denmark) developed tesofensine in the early 2000s as a treatment for Alzheimer's and Parkinson's disease, partnering with Boehringer Ingelheim. The idea was that boosting dopamine, norepinephrine, and serotonin in the CNS could address neurodegeneration. Phase II trials in AD and PD (2004-2007) failed to meet efficacy endpoints for either condition. But researchers kept noticing that participants were losing weight, consistently, across all trial arms. Boehringer Ingelheim returned the rights and NeuroSearch pivoted to obesity. The Phase IIb TIPO-1 trial (Lancet 2008, PMID: 18950853) enrolled 203 patients with BMI 30-40 and tested three doses over 24 weeks. The 0.5 mg dose produced 9.2% placebo-subtracted weight loss. At the time, that was roughly double any FDA-approved obesity drug. The 1.0 mg dose pushed weight loss to 10.6% but caused a 6.8/5.8 mmHg blood pressure increase and was dropped. The heart rate problem is what stalled US development. Even at 0.5 mg, heart rate increases 7-8 bpm above baseline and stays elevated throughout treatment. For a regulatory agency looking at long-term obesity treatment (potentially years or decades), a persistent heart rate increase is a red flag. This is the same concern that sank other sympathomimetic obesity drugs in the past. Saniona acquired the rights from NeuroSearch in 2014 and partnered with Medix for Latin American development. The Phase 3 Viking study (Mexico, 2018) met its primary and secondary endpoints. Medix filed with Mexico's COFEPRIS but approval has been withheld with ongoing discussions. Saniona is also developing Tesomet, a combination of tesofensine with metoprolol (a beta-blocker) for Prader-Willi syndrome. The metoprolol is specifically included to counteract the heart rate and blood pressure elevation. The FDA has provided guidance on that program. The drug interactions are the main clinical concern beyond cardiovascular effects. Tesofensine is absolutely contraindicated with MAOIs (serotonin syndrome and hypertensive crisis risk) and should not be combined with SSRIs, SNRIs, stimulants, or bupropion. It's metabolized primarily by CYP3A4, so strong CYP3A4 inhibitors (ketoconazole, ritonavir, grapefruit juice) will increase drug levels. In the US, tesofensine is available through compounding pharmacies with a prescription and through research chemical suppliers. It is not a peptide and was not affected by the FDA's peptide compounding restrictions. Estimated cost is $90-300/month depending on dose and source.
How Tesofensine Works
Tesofensine blocks reuptake of three neurotransmitters simultaneously by inhibiting SERT (serotonin), NET (norepinephrine), and DAT (dopamine) transporters. PET imaging confirmed dose-dependent striatal DAT occupancy of 18-77%. Serotonin enhancement promotes satiety. Norepinephrine increases sympathetic tone and thermogenesis. Dopamine reduces reward-seeking food behavior. It also silences GABAergic hypothalamic neurons involved in feeding. The appetite suppression is mediated specifically through alpha-1 adrenoceptors and dopamine D1 receptor pathways.
Receptor targets:
Benefits
- 9.2% placebo-subtracted weight loss at 0.5 mg in Phase IIb (double any approved drug in 2008)
- Reduces both appetite and increases resting energy expenditure
- Oral capsule, once daily (convenient dosing)
- Over 90% oral bioavailability
- Phase 3 Viking study met primary and secondary endpoints
- Long half-life (~9 days) provides stable drug levels
What Does the Research Say?
Tesofensine has solid Phase IIb data. Astrup et al. (Lancet 2008, PMID: 18950853) showed 9.2% weight loss at 0.5 mg over 24 weeks in 203 patients, about double any approved obesity drug at the time. Appel et al. (Eur Neuropsychopharmacol 2014, PMID: 24239329) confirmed dose-dependent DAT occupancy via PET imaging. Hansen et al. (Neuropsychopharmacology 2010, PMID: 20200509) identified the alpha-1/D1 appetite suppression pathway.
Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial
The Lancet, 2008 · DOI · PubMed
0.5 mg dose produced 9.2% placebo-subtracted weight loss in 24 weeks, approximately double any approved obesity drug at the time
Tesofensine, a novel triple monoamine re-uptake inhibitor: dopamine transporter occupancy as measured by PET
European Neuropsychopharmacology, 2014 · PubMed
PET imaging confirmed dose-dependent striatal dopamine transporter occupancy of 18-77%, confirming central dopaminergic mechanism
Tesofensine induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways
Neuropsychopharmacology, 2010 · PubMed
Appetite suppression mediated through alpha-1 adrenergic and D1 dopamine receptor pathways, not serotonergic pathways alone
PubMed evidence trail
Research sources used to frame this page
For Tesofensine, FormBlends checks the page topic against primary trials, systematic reviews, guidelines, and current PubMed-indexed literature where available. These citations are context, not a claim that every study applies to every patient.
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Primary STEP 1 trial source for semaglutide weight-management efficacy and adverse-event context.
PubMed
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance
Used for maintenance, discontinuation, and weight-regain discussions after semaglutide response.
PubMed
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial
Supports SELECT-context pages where semaglutide claims touch long-term weight change and cardiovascular-risk populations.
PubMed
Semaglutide for cardiovascular event reduction in people with overweight or obesity
Baseline SELECT source for cardiovascular-outcomes framing in people with overweight or obesity.
PubMed
Potential Side Effects
- Dry mouth (most frequent)
- Nausea, constipation, diarrhea
- Insomnia
- Headache
- Heart rate elevation: 7-8 bpm increase at 0.5 mg (range 5-15 bpm)
- Blood pressure at 0.5 mg: 1-3 mmHg increase (minimal)
- Blood pressure at 1.0 mg: +6.8/+5.8 mmHg (this dose was dropped)
- Elevated heart rate persists throughout treatment
Drug Interactions
| Compound | Interaction | Severity |
|---|---|---|
| MAOIs (monoamine oxidase inhibitors) | Risk of serotonin syndrome and hypertensive crisis. Absolute contraindication. | major |
| SSRIs and SNRIs (Zoloft, Prozac, Effexor, Cymbalta) | Serotonin syndrome risk from overlapping serotonergic mechanisms. | major |
| CYP3A4 inhibitors (ketoconazole, ritonavir, grapefruit juice) | Will increase tesofensine levels given its CYP3A4 metabolism. Monitor closely. | moderate |
| Stimulants (amphetamines, methylphenidate, bupropion) | Additive sympathomimetic and dopaminergic effects. Increased cardiovascular risk. | major |
Who Is Tesofensine For?
Women
No sex-specific dosing adjustments established. Monitor for mood changes given serotonergic activity. Contraindicated in pregnancy (CNS-active agent with no reproductive safety data).
Adults Over 50
Cardiovascular monitoring is especially important. The 9-day half-life means effects persist for weeks after stopping. CYP3A4 metabolism may slow with age, potentially increasing drug levels. Kidney function should be assessed.
Athletes
Not on WADA prohibited list, but its stimulant-like profile (NE/DA reuptake inhibition) could warrant future monitoring. Heart rate elevation may complicate training zone programming.
Regulatory Status
FDA Approved
No
Compounding Legal
Yes
2026 HHS Status
Not a peptide; not affected by peptide compounding regulations
Tesofensine is not a peptide and was not affected by the FDA peptide compounding restrictions. It is a small-molecule pharmaceutical available through compounding pharmacies with a prescription and through research chemical suppliers.
Last verified: 2026-04-06
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