Tesofensine
Tesofensine (NS2330) is an investigational oral triple monoamine reuptake inhibitor — it blocks presynaptic reuptake of noradrenaline, dopamine, and serotonin — that produced substantial weight loss in a phase II obesity trial.
Trials tested 0.25, 0.5, and 1.0 mg once daily, with 0.5 mg the most-studied dose; development for general obesity was not carried through, so this catalog shows no recommended dose ladder.
Best for
Reference only, for adults researching investigational appetite-suppressant pharmacology. It is not an approved medication anywhere for general obesity, it has no long-term safety data, and it is not a reasonable self-directed weight-loss protocol — approved GLP-1 agents have vastly better evidence and physician oversight.
What to expect
Appetite suppression is reported early, but the trial endpoints were measured at 24 weeks. The compound has a long, multi-day elimination half-life, so blood levels accumulate for weeks after a dose change and adverse effects do not clear quickly on stopping.
Pairs with
Nothing, on a self-directed basis. The one combination studied clinically is Tesomet, a fixed 0.5 mg tesofensine / 50 mg metoprolol combination in which the beta-blocker was added specifically to blunt the cardiovascular effects — which tells you what the underlying risk is. It must not be combined with SSRIs, SNRIs, MAOIs, or other serotonergic agents, or with stimulants.
Oral, once daily. The published trial range is 0.25-1.0 mg per day; the phase II obesity trial randomized patients to 0.25 mg, 0.5 mg, or 1.0 mg daily for 24 weeks, and 0.5 mg was the dose the authors carried forward. Reported research protocols start at 0.25 mg. Because development was halted and no long-term safety data exists, the app deliberately shows no recommended dose ladder for this compound — the numbers are a record of what trials used, not a suggested regimen.
No research dose is presented for Tesofensine — the goodtides app and Dose Calc present none either.
A research reference, not a prescription.
Tesofensine is a small-molecule inhibitor of the presynaptic transporters for noradrenaline, dopamine, and serotonin — a triple reuptake inhibitor, or SNDRI. It was originally developed for Parkinson's and Alzheimer's disease, failed in those indications, and was repurposed when weight loss appeared as a side effect.
A later, much smaller randomized trial of Tesomet (0.5 mg tesofensine plus 50 mg metoprolol) in 21 adults with hypothalamic obesity found an additional 6.3% weight loss versus placebo over 24 weeks with no significant heart-rate or blood-pressure difference, though sleep disturbance, dry mouth, and headache were markedly more common on treatment and one participant discontinued for exacerbated pre-existing anxiety.
Raising synaptic monoamines in hypothalamic and mesolimbic circuits suppresses appetite and increases energy expenditure; more recent rodent work has traced part of the effect to silencing of GABAergic neurons in the lateral hypothalamus. The pivotal human data is a 2008 phase II randomized, double-blind, placebo-controlled trial across five Danish obesity centres: 203 patients with a BMI of 30-40 were placed on an energy-restricted diet and randomized to 0.25 mg, 0.5 mg, 1.0 mg, or placebo once daily for 24 weeks.
Mean weight loss was 2.0% on diet plus placebo, versus 4.5%, 9.2%, and 10.6% on the three ascending doses. The most common adverse events were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia.
Blood pressure did not rise significantly at 0.25 mg or 0.5 mg, but heart rate increased by 7.4 beats per minute in the 0.5 mg group. The authors explicitly stated their efficacy and safety findings needed confirmation in phase III — confirmation that did not follow for general obesity.
PubMed's record for this trial also carries a 2013 Lancet expression of concern, which should be weighed when reading it. Tesofensine is a CYP3A4 substrate with a long elimination half-life, which makes it vulnerable to interaction with CYP3A4 inhibitors.
- Half-life
- Long — characterized in population-pharmacokinetic work as a long-elimination-half-life compound, on the order of days
- Peak
- Not well characterized in public sources; dosed once daily in all published trials
- Absorption
- Oral; CYP3A4-metabolized with enterohepatic recirculation described in PK modelling
- Bioavailability
- Not established in published sources
References4
- Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial
- Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity
- Semi-mechanistic population pharmacokinetic drug-drug interaction modelling of a long half-life substrate and itraconazole
- PubChem - Tesofensine Compound Summary, CID 11370864
Log every dose, count every vial, and verify your batches — free in the goodtides app.
This page is educational reference material about compounds studied in research settings. It is not medical advice, and nothing here is a recommendation to buy, possess, or use any compound. Research findings described are from published literature; individual compounds may not be approved for human use. Talk to a licensed clinician about anything that affects your health.