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Metabolic & GLP-1 · Reference monograph

Non-peptide triple monoamine reuptake inhibitor

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Tesofensine (NS2330) is a small-molecule, non-peptide inhibitor of the presynaptic reuptake transporters for noradrenaline, dopamine and serotonin. It was originally developed by the Danish company NeuroSearch as a candidate for Parkinson's disease and Alzheimer's disease. Neurology trials did not support those uses, but investigators noted reductions in body weight among participants, which redirected development toward obesity.

A phase 2 obesity trial published in The Lancet in 2008 drew wide attention to the compound, and development later passed to Saniona, which also studied tesofensine combined with the beta-blocker metoprolol in hypothalamic obesity and Prader-Willi syndrome. Tesofensine is not approved by the FDA or EMA, though it has reached limited registration elsewhere. Because it is not a peptide, it sits somewhat apart from most compounds in this catalogue; it is included for researchers studying central appetite regulation, monoamine transporter pharmacology and energy balance. Its cardiovascular profile, including effects on heart rate and blood pressure, has been an important consideration throughout its clinical development.

Mechanism studied

  1. Tesofensine
  2. NA / DA / 5-HT reuptake
  3. Central appetite control
  4. Weight endpoints

Tesofensine binds the noradrenaline transporter (NET), dopamine transporter (DAT) and serotonin transporter (SERT), inhibiting reuptake and increasing synaptic concentrations of all three monoamines. Rodent studies suggest its effects on food intake depend substantially on enhanced noradrenergic signalling via alpha-1 adrenoceptors and dopaminergic signalling via D1 receptors in hypothalamic circuits. Electrophysiological work in lateral hypothalamic GABAergic neurons has also implicated suppression of hedonic feeding. Some studies have suggested a modest increase in energy expenditure in addition to reduced intake. Sympathetic activation from noradrenaline reuptake inhibition accounts for heart-rate effects, which motivated the combination with metoprolol.

Research highlights

  • 01Originally developed by NeuroSearch as NS2330 for neurodegenerative disease before weight effects were observed.
  • 02A 2008 phase 2 trial in The Lancet established tesofensine as an obesity research candidate.
  • 03Rodent pharmacology identifies adrenergic alpha-1 and dopamine D1 receptor involvement in its effects on food intake.
  • 04Saniona investigated a tesofensine-metoprolol combination in hypothalamic obesity and Prader-Willi syndrome.
  • 05Open questions concern long-term cardiovascular safety, the abuse potential of dopaminergic agents and comparison with incretin-based approaches.

Latest published research

56 papers on PubMed →

  1. Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine

    Krug O et al. · Drug testing and analysis · 2026 Sep · PMID 42320973

  2. Structural basis for pharmacotherapeutic action of triple reuptake inhibitors

    Li Y et al. · Nature communications · 2025 Dec 14 · PMID 41392177

  3. Sex-specific effects of appetite suppressants on stereotypy in rats

    Lopez A et al. · PloS one · 2025 · PMID 40554466

  4. Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons

    Perez CI et al. · PloS one · 2024 · PMID 38656972

  5. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity

    Huynh K et al. · European journal of endocrinology · 2022 May 9 · PMID 35294397

  6. New insights into potential nutritional effects of dietary saponins in protecting against the development of obesity

    Jeepipalli SPK et al. · Food chemistry · 2020 Jul 15 · PMID 32151922

  7. Anorectic state of obesity medications in the United States. Are leaner times ahead?

    Li X et al. · Expert opinion on pharmacotherapy · 2020 Feb · PMID 31762335

  8. Centrally Acting Agents for Obesity: Past, Present, and Future

    Coulter AA et al. · Drugs · 2018 Jul · PMID 30014268

Live feed from PubMed (NCBI) for “Tesofensine”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

13 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Tesofensine”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Astrup et al., 2008 — Lancet 372:1906–1913
  2. [2]PubMed — reviews on tesofensine and obesity

FAQ

  • No. Tesofensine is a small-molecule phenyltropane derivative that acts on monoamine transporters. It is included in this catalogue because it is widely discussed in obesity and appetite research alongside peptide hormones, but its chemistry and pharmacology are distinct.

  • Inhibiting dopamine reuptake can enhance dopaminergic signalling, which is reduced in Parkinson's disease. Early trials did not demonstrate sufficient efficacy for neurological indications, but the weight changes recorded in those studies led researchers to investigate the compound in obesity.

  • Tesofensine is not approved by the US FDA or the European Medicines Agency. Limited registration has been reported in other markets. In all other contexts it remains an investigational compound for research use.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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