Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Tesofensine — also called NS2330 — is a small-molecule triple monoamine reuptake inhibitor. It blocks the presynaptic reuptake of serotonin, norepinephrine, and dopamine, raising synaptic levels of all three. It is included in this reference library because it is increasingly marketed alongside peptides in compounded weight-management products in some markets, but it is not a peptide and does not act on receptors used by the rest of this category.
The molecule is an orally bioavailable tablet, originally formulated at 0.125, 0.25, 0.5, and 1.0 mg doses for once-daily administration.
History
NeuroSearch, a Danish biotech, developed tesofensine in the late 1990s for Parkinson's disease and Alzheimer's disease, on the rationale that boosting dopaminergic and noradrenergic tone might compensate for neurodegenerative dopamine loss. Phase II trials in Parkinson's and Phase II/III trials in Alzheimer's reported negative results on the primary cognitive and motor endpoints, with one notable side effect: patients consistently lost weight.
NeuroSearch repurposed the molecule for obesity. The pivotal Phase II trial — Astrup et al. 2008 in The Lancet — enrolled 203 obese patients across five Danish centers and tested 0.25, 0.5, and 1.0 mg daily for 24 weeks. Weight loss was dose-dependent: 4.5%, 9.2%, and 10.6% respectively, compared with 2.0% on placebo. Cardiovascular signals — elevated heart rate, mood changes, sleep disruption — were also dose-dependent. The Lancet later issued an expression of concern about aspects of the 2008 trial data.
A Phase III program in obesity was planned but not completed under NeuroSearch. The rights were later acquired by Saniona, and the molecule was eventually licensed to Medix in Mexico, which secured approval there in 2023 under the brand name Nupelev. No active program exists in the United States or Europe.
Regulatory status
Tesofensine is approved in Mexico (2023) for obesity, marketed as Nupelev. It is not approved by the FDA or the European Medicines Agency. No active U.S. or European clinical program is registered.
Because tesofensine is a small molecule rather than a peptide, the FDA's 503A and 503B compounding pathways for peptides do not apply. There is no legal compounding pathway for tesofensine in the United States.
The World Anti-Doping Agency has not specifically listed tesofensine but it falls under the broader stimulant class S6.
Mechanism
Published mechanism papers describe tesofensine as a triple monoamine reuptake inhibitor — blocking the serotonin transporter (SERT), the norepinephrine transporter (NET), and the dopamine transporter (DAT). The 2012 Gilbert et al. paper in Obesity characterized the appetite-suppressing component as primarily indirect stimulation of α1-adrenoceptors and dopamine D1 receptors in central feeding circuits — distinct from the GLP-1 pathway used by semaglutide and tirzepatide.
The combination of dopamine and norepinephrine reuptake inhibition is responsible for both the appetite suppression and the cardiovascular effects (elevated heart rate, modest blood pressure increase) reported in trials.
Half-life and dosing intervals
Tesofensine has an unusually long plasma half-life — published estimates put it at approximately 9 days. The long half-life enables once-daily oral dosing but means steady state is not reached for 4 to 6 weeks, and dose escalation is correspondingly slow. After discontinuation, the drug remains detectable for weeks.
In the Astrup Phase II trial, doses were 0.25, 0.5, and 1.0 mg daily, with the 0.5 mg dose described as producing the best weight-loss-to-side-effect ratio. The Nupelev label in Mexico specifies oral once-daily dosing in a similar range.
Reconstitution example
Tesofensine is an orally bioavailable small molecule and is not reconstituted from a lyophilized vial — it is supplied as tablets or capsules.
Where it is sold as a research powder in 0.25, 0.5, or 1 mg increments, doses are typically managed by milligram weight per capsule rather than by syringe. A 0.5 mg capsule once daily corresponds to the most-studied dose from the Astrup trial. A 0.25 mg capsule is the lowest practical starting dose described in published research. Vial's tracking tools accept oral mg input directly when the route is set to oral.
What to know
- Not a peptide. Tesofensine is a small-molecule triple monoamine reuptake inhibitor, included in this reference set because it is increasingly marketed alongside peptide weight-management products.
- Approved only in Mexico. The 2023 Nupelev approval is the only active regulatory authorization. No FDA or EMA approval exists.
- Cardiovascular signals. Phase II trials documented dose-dependent heart rate increases (around 7 bpm at 0.5 mg) and blood pressure changes. Mood changes and sleep disruption were also dose-dependent.
- Long half-life. Steady state is not reached for 4 to 6 weeks and the drug remains detectable for weeks after discontinuation — a property to plan around if discontinuation is needed.
- Reported side effects in the Astrup and Gilbert trials: dry mouth, insomnia, constipation, headache, dizziness, increased heart rate, modest blood pressure increase, and mood changes. The Lancet issued a 2013 expression of concern regarding aspects of the 2008 data.
- Storage. Tablets and capsules should be stored at room temperature, protected from light and moisture, per the supplier or manufacturer label.
Sources
- 1.Astrup A et al. (2008). Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. The Lancet.
- 2.Gilbert JA et al. (2012). Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha-1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Obesity (Silver Spring).
- 3.Bello NT, Zahner MR (2009). Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity. Current Opinion in Investigational Drugs.
- 4.Doggrell SA (2009). Tesofensine — a novel potent weight loss medicine. Expert Opinion on Investigational Drugs.