Tesofensine

Not a peptide. Tesofensine is a small-molecule drug — a triple monoamine reuptake inhibitor acting on the brain's serotonin, noradrenaline and dopamine systems. It is included because it is frequently discussed and sold alongside peptides for weight loss and people search for it here. The same evidence standards apply.

NS2330; Tesomet (fixed-dose combination with metoprolol)

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Tesofensine has been reported as approved for obesity in Mexico † and is unapproved everywhere else, where it circulates as a grey-market research chemical. Its effects on heart rate, blood pressure and mood are the central safety issue.

Summary

Class: Small-molecule triple monoamine reuptake inhibitor (serotonin, noradrenaline, dopamine); a phenyltropane derivative originally developed for Alzheimer's and Parkinson's disease
Mechanism: Raises synaptic levels of three appetite- and mood-related neurotransmitters, suppressing appetite and modestly raising energy expenditure
Routes studied: Oral once daily
Dose range reported: Phase 2 (TIPO-1): 0.25, 0.5 and 1.0 mg daily for 24 weeks. Phase 3 (Viking): 0.25 and 0.5 mg daily. Mexican approval reportedly 0.25–0.5 mg daily †. Community-reported: 0.25–0.5 mg daily; the 1 mg dose was dropped from development because of blood-pressure effects
Half-life: Very long: roughly 8–9 days (~220 hours), so a daily dose accumulates over weeks and effects persist for weeks after stopping
Storage: Tablets/capsules: room temperature, dry, protected from light
Regulatory status: Reported approved in Mexico (2020–2021, COFEPRIS, marketed by Medix) †; not approved in the US, EU, UK, Australia or South Africa

Doses are as reported in studies or by the community — never recommendations.

1What it is

Tesofensine was developed in the late 1990s by the Danish company NeuroSearch as a treatment for Alzheimer's and Parkinson's disease. Those trials failed, but researchers noticed that participants lost weight. NeuroSearch redirected it to obesity, and a 2008 phase 2 trial reported weight loss roughly twice that of any obesity drug then on the market. Development then stalled for years for financial and regulatory reasons; Saniona (another Danish company) acquired it, ran phase 3 trials in Mexico with the local partner Medix, and reported Mexican regulatory approval in the early 2020s †.

Chemically it belongs to the same family as some cocaine-derived research compounds (phenyltropanes), but it binds the three transporters with roughly balanced affinity and a slow onset and very long , which blunts any euphoric effect. It is not a peptide, not a hormone analogue and not injectable. It appears here because it is sold by the same grey-market channels as peptides and bundled into "weight loss stacks".

2How it's thought to work

Appetite. increased noradrenaline and serotonin in hypothalamic circuits reduce hunger and increase fullness; dopamine changes reduce food reward.

Energy expenditure. a small increase in thermogenesis has been reported, attributed to noradrenergic and dopaminergic effects.

Blood pressure and heart rate. noradrenaline reuptake inhibition raises both — the dose-limiting problem, and the reason the Tesomet combination adds the beta-blocker metoprolol.

Mood and sleep. monoamine effects produce the insomnia, dry mouth and agitation reported in trials, and raise theoretical concerns about mood changes in susceptible people.

Not a peptide: a small molecule blocking the reuptake of noradrenaline, dopamine and serotonin at once, so all three stay in the synapse. Appetite falls as a consequence. Its cardiovascular effects are the reason development has been difficult.Schematic — not to scale

3What the research shows

Weight loss in obesity

TIPO-1 (n=203, 24 weeks, with diet and exercise) reported mean weight loss of 4.5% (0.25 mg), 9.2% (0.5 mg) and 10.6% (1.0 mg) versus 2.0% with placebo, a placebo-adjusted loss of roughly 2.5–8.6% of body weight (Astrup 2008, Lancet). At the time this was about double the effect of sibutramine or rimonabant. Dry mouth, insomnia, nausea and constipation were common, and heart rate rose by about 7–8 bpm at 0.5 mg; blood pressure rose significantly at 1.0 mg. [1][2]

Graded A/B

Phase 3 (Viking programme)

Saniona's Viking 1 trial in Mexico (n≈372, 24 weeks, 0.25 and 0.5 mg) reported weight loss of about 6–9% versus ~1% placebo †, with a safety profile described as consistent with phase 2. Results were announced by the company and presented at congresses; full peer-reviewed publication should be verified †. A second trial (Viking 2) was planned †.

Graded A/B

Hypothalamic obesity and Prader-Willi syndrome (Tesomet)

Tesomet (tesofensine 0.5 mg + metoprolol 50 mg) was tested in small randomised trials in hypothalamic obesity (n=21; weight loss ~6% vs placebo gain over 24 weeks; Huynh 2022, eClinicalMedicine) and in Prader-Willi syndrome (small phase 2 with hyperphagia improvements †). Saniona paused the programme for business reasons in 2022–2023 †. [5]

Graded A (negative/weak)

Alzheimer's and Parkinson's disease

A phase 2 in Parkinson's found a small, dose-dependent improvement in motor scores at 24 weeks that was not considered clinically compelling (Rascol 2008, Arch Neurol). Alzheimer's trials did not show cognitive benefit. [3]

Not gradednone

Head-to-head with GLP-1 agonists

No comparison exists. Its 24-week weight loss (~9% at 0.5 mg) is in the range of semaglutide at a similar timepoint, but without any cardiovascular outcome data, and with the opposite effect on heart rate and blood pressure.

4Reported side effects and interactions

Literature-reported

Literature (common). dry mouth (the most frequent, often >30%), insomnia, nausea, constipation, dizziness, headache, agitation or irritability, increased heart rate (~7–8 bpm at 0.5 mg), and blood pressure rises that were significant at 1.0 mg and borderline at 0.5 mg. Discontinuations for adverse events increased with dose. Mood changes were monitored closely given the history of rimonabant; no suicidality signal was reported in the published trials, but the numbers are small.

Serious / theoretical. sustained increases in heart rate and blood pressure with a drug that has no cardiovascular outcome trial; this is the class problem that removed sibutramine from the market (SCOUT trial, 2010). Potential for serotonin syndrome with other serotonergic drugs; dopaminergic effects raise theoretical concerns about dependence (considered low because of slow kinetics, but not studied for misuse), psychosis in susceptible individuals and interactions with stimulants. Very long means adverse effects take weeks to wash out. Not studied in pregnancy.

Community-reported

marked appetite suppression, dry mouth, insomnia (often dosed early morning for this reason), jitteriness in the first weeks, elevated heart rate, occasional reports of anxiety or low mood; some report tolerance to the appetite effect after several months.

Interactions. MAO inhibitors, SSRIs/SNRIs, tramadol, triptans, St John's wort and other serotonergic agents (serotonin syndrome risk); stimulants and decongestants (additive cardiovascular effects); antihypertensives may need adjustment; CYP3A4 inhibitors/inducers may alter exposure †. Metoprolol is the deliberate combination in Tesomet.

Markers researchers commonly monitor

Following the trial protocols and the pharmacology:

Marker	Why it's watched
Resting heart rate and blood pressure	the dose-limiting effects; home monitoring before starting and weekly thereafter is the single most useful measure.
ECG	a baseline is reasonable for anyone with cardiac history, given sympathomimetic effects and the absence of outcome data.
Mood, anxiety and sleep log	monoaminergic drugs can change these; the trials screened for depression and monitored it.
Weight and waist circumference	the intended outcome.
Fasting glucose, HbA1c and lipid panel	improved modestly with weight loss in TIPO-1; useful tracking.
CMP and liver enzymes	general baseline for a drug with no long-term safety data.
Medication review	for serotonergic and stimulant interactions; not a lab test but the main safety step.

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Oral tablets or capsules, usually 0.25 mg or 0.5 mg, taken once daily, in trials in the morning. Store at room temperature away from light and moisture. Because of the ~9-day , steady state takes roughly a month to reach and effects outlast dosing by weeks; community "cycling" protocols rarely account for this. Grey-market capsules of unknown identity are the norm outside Mexico. No applies.

6Commonly studied alongside

Metoprolol (Tesomet fixed-dose combination, to counter heart-rate effects). Nothing else in the literature. Community stacks pair it with GLP-1 agonists, AOD-9604, 5-Amino-1MQ (profile 69) or MOTS-c; none of these combinations has been studied, and pairing a sympathomimetic with any agent that also raises heart rate deserves particular caution.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; no active US development programme †. Sold as a research chemical, which is unlawful for human consumption
European Union	Not authorised; EMA filing never submitted †
United Kingdom	Not licensed
Australia	Not approved; appears on TGA warnings for imported weight-loss products †
South Africa	Not registered
Mexico	COFEPRIS approval for obesity reported 2020–2021, marketed by Medix †
Sport	Not specifically named by WADA. Monoamine reuptake inhibitors with stimulant-like effects may fall under S6 (stimulants) by the "similar biological effect" clause, and as a non-approved substance outside Mexico under S0 †

8Open questions

Cardiovascular safety over the long term — the question that ended sibutramine and that no tesofensine trial has answered.
Durability of weight loss beyond 24 weeks and regain after stopping, given the long .
Whether Tesomet adequately neutralises the heart-rate effect, and the future of the hypothalamic obesity programme.
Any misuse or dependence potential with chronic dosing.
Independent confirmation of the Mexican phase 3 results in peer-reviewed form.

9References

1Astrup 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 (TIPO-1). Lancet. PubMed · DOI
2Astrup A et al. (2008). Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease. Obesity. PubMed · DOI
3Rascol O et al. (2008). Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS study. Arch Neurol. PubMed · DOI
4Sjödin A et al. (2010). The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes. PubMed · DOI
5Huynh K et al. (2022). Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity. eClinicalMedicine [verify journal]. DOI
6Saniona (2018–2021). Viking 1 phase 3 results and Mexican regulatory announcements — company releases [verify peer-reviewed publication]. PubMed
7James WPT et al. (2010). Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects (SCOUT). NEJM — cited for class context on monoamine reuptake inhibitors and cardiovascular risk. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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