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Tesofensine

Updated · 26 sources · Editorial policy

Tesofensine (research code NS2330) is an experimental oral drug that blocks the reuptake of three brain chemical messengers: serotonin, norepinephrine and dopamine. It was first tested in Parkinson’s and Alzheimer’s disease. It did not meet its efficacy goals in either, but patients lost weight, so it was redeveloped as an obesity drug (Astrup et al., Obesity 2008; Coulter et al., Drugs 2018).

The most important fact: tesofensine has never received full marketing approval. Its developer’s Mexican partner has applied for approval in Mexico, but as of 2026 the application was still under review (Saniona; Krug et al., Drug Test Anal 2026). The main published obesity trial carries a 2013 expression of concern from The Lancet. Even so, tesofensine is sold online as a “dietary supplement,” and it is banned in competition by the World Anti-Doping Agency (WADA).

This page summarizes what the published clinical trials and regulators report. It is for education only and is not medical advice.

Property Detail
Drug class Triple monoamine reuptake inhibitor (serotonin, norepinephrine and dopamine)
Other names NS2330
Route Oral, once daily in trials
Doses studied 0.125–1.0 mg/day in phase 2 trials; 2.0 mg/day for 1 week in one short mechanism study
Half-life ≈234 h (≈10 days) in a population model; active metabolite M1 ≈374 h
Time to steady state 6–12 weeks
Approval status Not approved anywhere; Mexican application under review
US controlled-substance status Not listed in Schedules I–V (21 CFR 1308.11–1308.15)
WADA status Prohibited in competition (S6.B specified stimulant)

What it is

Tesofensine’s chemical name is (1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane: formula C₁₇H₂₃Cl₂NO, molecular weight 328.3 g/mol (PubChem). It is a small synthetic molecule, not a peptide or a steroid.

It works by blocking the transporters that pull three monoamines back into nerve cells after release. This leaves more of each in the gap between nerve cells:

  • Norepinephrine: drives alertness, heart rate and blood pressure.
  • Dopamine: involved in reward, motivation and movement.
  • Serotonin: involved in mood and satiety (feeling full).

A PET brain-imaging study in people showed dose-dependent blockade of the dopamine transporter. Striatal occupancy ranged from 18% to 77% at doses of 0.125–1 mg. About half of the maximum effect was reached at 0.25 mg (Appel et al., Eur Neuropsychopharmacol 2014).

In obese rats, the appetite-suppressing effect was almost fully blocked by prazosin (an α1-adrenergic blocker) and partly blocked by a dopamine D1 blocker. This suggests, in rats, that the drug lowers food intake mainly through norepinephrine and dopamine signaling (Axel et al., Neuropsychopharmacology 2010). Whether the same holds in humans has not been shown.

Its pharmacological profile has been compared with that of sibutramine, an older weight-loss drug (Doggrell, Expert Opin Investig Drugs 2009).

Pharmacokinetics

The best human data come from a population model built on 320 patients with Alzheimer’s disease who took the drug for 14 weeks (Lehr et al., Br J Clin Pharmacol 2007). Its introduction also summarizes earlier unpublished studies in healthy volunteers:

Parameter Value
Oral bioavailability Over 90%
Time to peak plasma level 6–8 h
Effect of food No clinically relevant difference fed vs fasted
Main metabolic route CYP3A4 (a liver enzyme) converts it to the desalkyl metabolite M1
Half-life, parent drug 234 h in the model (≈200 h in earlier studies)
Half-life, M1 metabolite 374 h in the model (≈400 h in earlier studies)
Time to steady state 6–12 weeks
Effect of sex and kidney function Women with impaired kidney function (creatinine clearance 35.6 mL/min) had 62% higher exposure than men with normal kidneys

M1 is pharmacologically active. In mice it was about 4–5 times less potent than the parent drug at the dopamine transporter, but it builds up to higher levels (Lehr et al., Br J Pharmacol 2008).

The very long half-life matters in practice. A drug with a half-life near 10 days takes weeks to reach steady levels, and weeks to clear after it is stopped. Side effects can therefore persist well after the last dose.

In an anti-doping study, six volunteers took a single 483 μg dose from a commercial supplement. Peak urine levels of the parent drug were 1–4 ng/mL, reached 4–46 h after intake. The drug and its metabolites stayed detectable for up to 500 h, with marked differences between people (Krug et al., Drug Test Anal 2026).

Regulatory status

  • No approval. No regulator has granted tesofensine full marketing authorization (Krug et al., Drug Test Anal 2026).
  • Mexico. Saniona’s partner Medix submitted an application to COFEPRIS, Mexico’s drug regulator. A COFEPRIS technical committee gave a favorable opinion in February 2023 (Saniona). In November 2024 Saniona announced that Medix had not received approval, and stated that the decision was not based on the full data package (Saniona press release, 2024). Saniona’s pipeline page still lists the application as submitted, not approved.
  • United States. Tesofensine is not named in any of the federal controlled-substance schedules (21 CFR part 1308). Not being scheduled does not make it an approved drug or a legal dietary supplement ingredient.
  • Sport. WADA lists tesofensine by name among the S6.B specified stimulants, prohibited in competition (WADA 2026 Prohibited List).

What the research shows

Obesity: the TIPO-1 phase 2 trial

The key obesity trial randomized 203 adults with obesity (BMI 30–40) at five Danish centers to placebo or tesofensine 0.25, 0.5 or 1.0 mg once daily for 24 weeks. Everyone also followed an energy-restricted diet. 161 participants (79%) completed the trial (Astrup et al., Lancet 2008; ClinicalTrials.gov NCT00394667):

Arm n randomized Mean weight loss at 24 weeks (diet included) Difference vs placebo
Placebo + diet 52 2.0% —
Tesofensine 0.25 mg 52 4.5% ≈2.5 percentage points
Tesofensine 0.5 mg 50 9.2% ≈7.2 percentage points
Tesofensine 1.0 mg 49 10.6% ≈8.6 percentage points

All three doses beat placebo (p under 0.0001). Heart rate rose by 7.4 beats per minute at 0.5 mg. Blood pressure did not rise significantly at 0.25 or 0.5 mg (Astrup et al., Lancet 2008), but a later review notes that it did rise at 1.0 mg (Coulter et al., Drugs 2018).

About the “twice the weight loss of other drugs” claim. This comes from the 2008 trial’s own conclusion. It was one 24-week phase 2 trial of about 50 people per arm. In 2013 The Lancet published an expression of concern about the paper (Lancet 2013), and the authors replied in a letter titled “Under-reporting of adverse effects of tesofensine” (Astrup et al., Lancet 2013). The trial’s own authors said the results needed confirmation in phase 3 trials.

Phase 3 in Mexico

Medix ran a phase 3 program in 372 people with obesity testing 0.25 and 0.5 mg daily for 24 weeks. According to Saniona, it showed an average weight loss of about 10% (Saniona press release, 2024). We could not find these results in a peer-reviewed journal, so the company summary cannot be checked against the full data.

How it causes weight loss

  • Appetite. In 32 overweight men given 2.0 mg/day for 7 days and then 1.0 mg/day for 7 days, tesofensine raised feelings of satiety and fullness. The men lost 1.8 kg more than on placebo in 2 weeks, even though they were told to keep eating as usual (Sjödin et al., Int J Obes 2010).
  • Energy use. Total 24-hour energy expenditure did not change. Night-time energy expenditure was 4.6% higher, and fat burning rose by 18 g per day (same study).
  • Fading satiety. In the TIPO-1 participants, satiety scores were raised at week 12 but had waned by week 24 as weight fell. After the drug was stopped, satiety scores returned to baseline (Gilbert et al., Obesity 2012).

Parkinson’s and Alzheimer’s disease

Tesofensine failed in its original indications:

  • Early Parkinson’s disease. In 261 untreated patients, 0.25–1.0 mg/day for 14 weeks did not improve symptom scores more than placebo (Hauser et al., Mov Disord 2007).
  • Advanced Parkinson’s disease. Modest gains at single doses (0.25 or 0.5 mg) with no clear dose-response; gastrointestinal and neuropsychiatric side effects rose at higher doses (Rascol et al., Arch Neurol 2008).
  • Alzheimer’s disease. A 14-week phase 2 proof-of-concept trial in 430 patients was negative (Lehr et al., AAPS J 2010).

A pooled analysis of four of these 14-week trials (740 on tesofensine, 228 on placebo), done without any diet program, found dose-related weight loss and rising heart rate (Astrup et al., Obesity 2008):

Daily dose Weight change at 14 weeks Heart rate change
Placebo +0.5% −0.4 bpm
0.125 mg −0.5% +2.1 bpm
0.25 mg −0.9% +4.2 bpm
0.5 mg −1.8% +6.0 bpm
1.0 mg −2.8% +6.8 bpm

Tesomet (tesofensine plus metoprolol)

To counter the heart-rate rise, the drug has been combined with metoprolol, a beta-blocker, as “Tesomet.” In a 24-week trial in 21 adults with hypothalamic obesity (obesity caused by damage to the hypothalamus), Tesomet (0.5 mg/50 mg) led to 6.3% more weight loss than placebo (95% CI 1.3–11.3), with no significant change in heart rate or blood pressure (Huynh et al., Eur J Endocrinol 2022). Follow-up phase 2 studies in hypothalamic obesity and Prader-Willi syndrome were withdrawn before enrolling anyone (NCT05147415; NCT05198362).

Side effects and risks

Common side effects

In TIPO-1 the most common drug-related side effects were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia (Astrup et al., Lancet 2008). In the small Tesomet trial, rates versus placebo were (Huynh et al., Eur J Endocrinol 2022):

Side effect Tesomet Placebo
Sleep disturbances 50% 13%
Dry mouth 43% 0%
Headache 36% 0%

Heart rate and blood pressure

A rise in heart rate is the most consistent finding: about +7 beats per minute at 0.5 mg in TIPO-1, and +2 to +7 beats per minute across doses in the neurology trials. A review of the clinical program called raised blood pressure and pulse rate the dose-limiting side effects (Coulter et al., Drugs 2018). No trial of tesofensine has been large or long enough to measure heart attacks or strokes.

Mood and psychiatric effects

Because tesofensine acts on serotonin, norepinephrine and dopamine, mood effects are expected. One evaluation of TIPO-1 noted more depressed mood at 0.5 mg (Doggrell, Expert Opin Investig Drugs 2009), and a later review noted more mood changes at 1.0 mg (Coulter et al., Drugs 2018). In the Tesomet trial, one patient with prior anxiety stopped treatment because of a serious worsening of anxiety (Huynh et al., Eur J Endocrinol 2022).

Abuse potential

In a single-dose crossover study in 52 recreational stimulant users, tesofensine’s subjective effects did not differ from placebo. They were lower than those of d-amphetamine and no greater than those of bupropion or atomoxetine (Schoedel et al., Clin Pharmacol Ther 2010). This was a single-dose study and does not address repeated use.

Drug interactions

Because CYP3A4 clears tesofensine, drugs that block this enzyme raise its levels. With the antifungal itraconazole, a model estimated a 38% drop in tesofensine clearance and a 63% rise in exposure (Lehr et al., Clin Pharmacokinet 2010).

Unknown long-term safety

The longest published follow-up is about 60 weeks, and that includes a drug-free gap and an uncontrolled open-label phase (Gilbert et al., Obesity 2012). The largest peer-reviewed obesity trial gave the drug to 151 people, and that paper later received an expression of concern.

Quality and contamination

Because tesofensine is not approved anywhere, products sold online come from outside the regulated drug supply. Anti-doping researchers bought a tesofensine “dietary supplement” online for their study and had to measure its actual content (483 μg per capsule) before use (Krug et al., Drug Test Anal 2026). Dose, purity and identity of such products are not verified by any regulator.

Key takeaways

  • An unapproved triple reuptake inhibitor. Tesofensine blocks reuptake of serotonin, norepinephrine and dopamine, and has no full marketing approval anywhere.
  • Real weight loss in a phase 2 trial. In TIPO-1, 0.5 mg/day with diet produced 9.2% weight loss at 24 weeks vs 2.0% on placebo, but that paper later received an expression of concern.
  • Very long half-life. About 10 days for the parent drug and longer for its active metabolite, so effects and side effects build up and clear slowly.
  • Heart rate is the main known risk. Pulse rose about 7 beats per minute at 0.5 mg, blood pressure rose at 1.0 mg, and mood changes were reported at higher doses.
  • Phase 3 data are not peer-reviewed. The Mexican phase 3 results are known only from company summaries.
  • Banned in sport. WADA lists it as an in-competition stimulant, and it remains detectable in urine for weeks.

Sources

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  2. Expression of concern—effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9873):1167. PubMed.
  3. Astrup A, Madsbad S, Breum L, et al. Under-reporting of adverse effects of tesofensine. Lancet. 2013;382(9887):127. PubMed.
  4. NeuroSearch A/S. Effect of tesofensine on weight reduction in patients with obesity. ClinicalTrials.gov identifier NCT00394667. ClinicalTrials.gov.
  5. Astrup A, Meier DH, Mikkelsen BO, et al. Weight loss produced by tesofensine in patients with Parkinson’s or Alzheimer’s disease. Obesity (Silver Spring). 2008;16(6):1363–1369. PubMed.
  6. Sjödin A, Gasteyger C, Nielsen AL, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond). 2010;34(11):1634–1643. PubMed.
  7. Gilbert JA, Gasteyger C, Raben A, et al. The effect of tesofensine on appetite sensations. Obesity (Silver Spring). 2012;20(3):553–561. PubMed.
  8. Appel L, Bergström M, Buus Lassen J, et al. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014;24(2):251–261. PubMed.
  9. Axel AM, Mikkelsen JD, Hansen HH. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Neuropsychopharmacology. 2010;35(7):1464–1476. PubMed.
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  11. Lehr T, Staab A, Tillmann C, et al. Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol. 2008;153(1):164–174. PubMed.
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  14. Hauser RA, Salin L, Juhel N, et al. Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson’s disease. Mov Disord. 2007;22(3):359–365. PubMed.
  15. Rascol O, Poewe W, Lees A, et al. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008;65(5):577–583. PubMed.
  16. Huynh K, Klose M, Krogsgaard K, et al. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity. Eur J Endocrinol. 2022;186(6):687–700. PubMed.
  17. Saniona. Study of Tesomet with open-label extension in subjects with hypothalamic obesity (HO). ClinicalTrials.gov identifier NCT05147415; and Study of Tesomet with open-label extension in subjects with Prader-Willi syndrome. NCT05198362. ClinicalTrials.gov; ClinicalTrials.gov.
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  25. US Drug Enforcement Administration. Schedules of controlled substances, 21 CFR part 1308. eCFR.
  26. World Anti-Doping Agency. The 2026 Prohibited List: International Standard. WADA 2026 Prohibited List.