Tesofensine (NS2330) is a small-molecule triple monoamine reuptake inhibitor, not a peptide. It appears on peptide supplier lists because it was one of the more effective weight-loss candidates of the pre-GLP-1 era, and researchers comparing appetite pathways still source it. This profile covers the mechanism, the clinical trial record from its NeuroSearch development programme, the reasons it never reached the market in the United States or Europe, and what the 33 suppliers on Peptides.SO currently charge.
> Research use only. Tesofensine sold through the suppliers listed here is a laboratory reagent for in-vitro and preclinical investigation. This profile summarises published studies; it is not a protocol for administration to humans or animals.
What tesofensine is
Tesofensine is a phenyltropane derivative developed by the Danish company NeuroSearch in the late 1990s as NS2330. It blocks the presynaptic transporters for noradrenaline, dopamine and serotonin, so it raises synaptic levels of all three monoamines at once. It was first tested in Alzheimer's and Parkinson's disease on the reasoning that monoamine deficits contribute to both. Those trials did not show the hoped-for neurological benefit, but patients lost weight, and the programme was redirected to obesity.
The molecule has a long half-life, which matters for how the trial results should be read: the population pharmacokinetic analysis Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease (PMID 17324246) fitted plasma data from 320 subjects and found low apparent clearances for both parent drug and its active metabolite M1, which means accumulation to steady state takes weeks and the effect of a given dose builds slowly.
Mechanism of action
Triple reuptake inhibition
The defining property is simultaneous inhibition of the dopamine transporter (DAT), the noradrenaline transporter (NET) and the serotonin transporter (SERT). Most antidepressants hit one or two; sibutramine, the closest marketed comparator before its withdrawal, hit NET and SERT with weaker DAT activity. Tesofensine has a stronger dopaminergic component.
How much of the DAT is actually occupied in humans was measured directly. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET (PMID 24239329) used [11C]βCIT-FE PET after 8–12 days of oral dosing and found striatal DAT occupancy varying between 18% and 77% across dose levels, with a maximum achievable occupancy of about 80%. The authors concluded that the dose-dependent weight loss seen in earlier trials was "in part mediated by an up-regulation of dopaminergic pathways".
Appetite suppression through downstream receptors
The rat pharmacology paper 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 (PMID 20200509) dissected which receptors carry the effect. In diet-induced obese rats the hypophagic response was blocked by an α1-adrenoceptor antagonist and by a dopamine D1 antagonist, but not by serotonergic antagonists, which places the appetite effect on the noradrenergic and dopaminergic arms rather than the serotonergic one.
More recent work has mapped the circuit. Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons (PMID 38656972) combined electrophysiological ensemble recordings with optogenetic and chemogenetic manipulation in mice and rats and found that tesofensine inhibits GABAergic neurons in the lateral hypothalamus, a population that normally drives feeding. The same study reported that the appetite effect was independent of taste aversion, that tesofensine prolonged weight loss induced by the serotonin precursor 5-HTP, and that it blocked the weight rebound that typically follows weight loss in rodents.
Energy expenditure
The human mechanism study The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men (PMID 20479765) treated 32 men for two weeks under conditions designed to hold body weight constant. Tesofensine still produced 1.8 kg of weight loss relative to placebo, increased satiety and fullness ratings, and raised 24-hour fat oxidation by 18 g. It did not change total 24-hour energy expenditure, although night-time expenditure was about 4.6% higher after adjustment for body composition. The authors' summary: "a pronounced effect on appetite sensations and a slight effect on energy expenditure at night".
Clinical trial record
The Lancet phase II obesity trial (TIPO-1)
The trial that made tesofensine's reputation is Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial (PMID 18950853), published in The Lancet in 2008. It randomised 203 obese patients (BMI 30–40) at five Danish centres to three tesofensine dose arms or placebo for 24 weeks alongside an energy-restricted diet; 161 (79%) completed.
Mean weight loss after 24 weeks was 2.0% with diet and placebo versus 4.5%, 9.2% and 10.6% in the low, middle and high tesofensine arms (p<0.0001). The most common adverse events were dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia. The two lower doses did not significantly raise blood pressure, but heart rate rose by 7.4 beats per minute in the middle arm. The authors suggested that the middle dose offered the best balance of weight loss against cardiovascular effects.
At the time this placed tesofensine well above orlistat and sibutramine. For context, semaglutide and tirzepatide have since produced larger placebo-subtracted losses in phase III, which is a large part of why tesofensine's programme lost commercial momentum; see the semaglutide research overview and the retatrutide profile for those data.
Weight loss in the neurology trials
Before obesity became the target, the effect was noticed in patients who were not trying to lose weight. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease (PMID 18356831) pooled four randomised trials (740 tesofensine, 228 placebo) run for 14 weeks with no diet programme. Weight change was +0.5% on placebo and −0.5%, −0.9%, −1.8% and −2.8% across the four ascending dose arms; in the obese subgroup the highest arm lost 3.7%, and the share of obese patients reaching 5% weight loss rose from 2.1% on placebo to 32.1%. Heart rate rose with dose, but blood pressure did not change. The authors put the placebo-subtracted loss at about 4% over 14 weeks with no diet or lifestyle programme, comparable to sibutramine, and noted that tesofensine was on that basis being redeveloped for obesity.
Parkinson's disease
Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease (PMID 17149725) enrolled 261 untreated early-PD patients. The highest dose was superior to placebo on total UPDRS at week 6, but the effect was not sustained, and the authors concluded that "at the dosages tested, NS 2330 did not provide significantly greater benefit than placebo". In advanced disease, the ADVANS study (PMID 18474731) found modest improvements in UPDRS II+III and in off-time at two of four doses but could not establish a dose-response relationship, and gastrointestinal and neuropsychiatric adverse events increased with dose.
Cardiovascular signal and the metoprolol combination
The heart-rate increase in TIPO-1 is the reason tesofensine's later development paired it with a beta-blocker (the combination was developed as Tesomet). The preclinical rationale is in Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats (PMID 23784901), which showed that co-administration of antihypertensives blocked the tachycardia and pressor effects in rats without reducing the hypophagic effect.
Regulatory status
Tesofensine has never been approved by the FDA or the EMA. Its current developer, Saniona, licensed Latin American rights to the Mexican company Medix, which pursued national registration for obesity; the status of that registration sits outside the peer-reviewed literature and should be checked against the COFEPRIS register directly. In the United States and the European Union tesofensine remains an investigational compound, which is why it is sold as a research chemical.
Research specifications
| Property | Value |
|---|---|
| Development code | NS2330 |
| Chemical class | Phenyltropane; triple monoamine reuptake inhibitor (DAT/NET/SERT) |
| Formula | C17H23Cl2NO |
| Molecular weight | 328.3 g/mol (free base) |
| Active metabolite | M1 (N-desmethyl tesofensine), long half-life |
| Common research formats | Capsules or tablets at sub-milligram unit strengths as labelled by the supplier; some suppliers list powder |
| Storage | Room temperature, dry, protected from light |
| Analytical check | HPLC-UV or LC-MS; verify against a reference standard, as the supplier market has no pharmacopoeial monograph |
Because tesofensine is an oral small molecule, it does not need reconstitution and has none of the cold-chain issues of peptides. That also means the peptide reconstitution guide does not apply; the relevant quality question is capsule content uniformity, which a certificate of analysis should state.
Tesofensine on Peptides.SO: supplier pricing
The platform tracks 43 tesofensine listings from 33 suppliers, price-checked through 25 September 2026. The median list price is $180, with an interquartile range of $150 to $249.99 and a full range of $60 to $500. Eleven of the 43 listings carry a discounted price.
This is an expensive product relative to the rest of the catalogue: the median tesofensine listing costs about 2.8 times the platform-wide median of a 5 mg BPC-157 vial ($65 across roughly 100 suppliers). The spread reflects pack size as much as supplier margin, since most listings are 30-, 60- or 90-count bottles at different unit strengths, so compare per-milligram rather than per-bottle.
- •Current offers and per-supplier comparison: tesofensine listings
- •Working out cost per milligram: cost calculator
- •Related supplier roundup: best GLP-1 research peptides for weight-loss studies
Comparison with related compounds
Sibutramine. A serotonin-noradrenaline reuptake inhibitor withdrawn in 2010 after the SCOUT trial showed excess cardiovascular events. Tesofensine has a stronger dopaminergic component and produced roughly twice sibutramine's weight loss in its phase II trial, but carries the same class-level concern about heart rate and blood pressure.
Bupropion. A noradrenaline-dopamine reuptake inhibitor with no serotonergic activity, marketed for obesity in fixed combination with naltrexone. Its weight effect is considerably smaller than tesofensine's; the difference is usually attributed to tesofensine's much higher DAT occupancy.
GLP-1 receptor agonists. Semaglutide and tirzepatide act peripherally and centrally through incretin receptors rather than monoamine transporters. They now define the efficacy bar and, unlike tesofensine, have cardiovascular outcome trials. Researchers comparing mechanisms sometimes pair tesofensine with GLP-1 agonists because the pathways are independent; the rodent 5-HTP data above (PMID 38656972) is the main published example of a tesofensine combination.
Frequently asked questions
Is tesofensine a peptide?
No. It is a small synthetic molecule taken orally. It is listed by peptide suppliers because the same research buyers want it for metabolic studies.
How effective was it in trials?
In the 24-week Lancet phase II trial (PMID 18950853), the highest dose arm lost 10.6% of body weight versus 2.0% on diet and placebo. That was roughly double what approved drugs achieved in 2008.
Why was it never approved in the US or EU?
The phase II heart-rate signal, the cost of the phase III programme that would have been needed, and the subsequent arrival of GLP-1 agonists with larger effects and outcome data. The literature does not contain a completed US or EU phase III trial.
Does it work through serotonin?
The rat receptor-blockade study (PMID 20200509) found the appetite effect ran through α1-adrenergic and D1 dopaminergic pathways, not serotonergic ones, even though SERT is inhibited.
What is Tesomet?
A fixed-dose combination of tesofensine with the beta-blocker metoprolol, developed to offset the heart-rate increase. The preclinical basis is the rat study above (PMID 23784901).
What should a certificate of analysis show?
Identity by LC-MS or HPLC against a reference standard, assay percentage, and for capsules, content uniformity. See the COA interpretation guide.
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This article is for educational and research purposes only. Tesofensine sold through the suppliers listed on Peptides.SO is a laboratory reagent and is not intended for human or animal use. Trial doses are reported here as published findings, not as guidance. Nothing on this page is medical advice.