Tesofensine

Tesofensine is a non-peptide small-molecule research compound, not a peptide, and the literature describes it as a triple monoamine reuptake inhibitor. Its free base formula is C17H23Cl2NO at 328.3 g/mol, and it is commonly isolated as the citrate salt at C23H31Cl2NO8 and 520.4 g/mol. The scaffold is a tropane, an 8-methyl-8-azabicyclo[3.2.1]octane ring, carrying a 3,4-dichlorophenyl group and an ethoxymethyl side chain, with defined stereochemistry at four centres, (1R,2R,3S,5S). It is assembled by conventional medicinal chemistry rather than peptide synthesis, and has none of the amide backbone a peptide is built from.

The compound also carries the development designation NS-2330, and both names appear in the literature for one molecule. Its major metabolite is recorded as M1, itself active at the same transporters, which complicates any reading drawn from the parent alone. Within transporter pharmacology it serves as a standard non-peptide reference blocker of the three monoamine carriers, and like several other small molecules it is often filed, incorrectly, alongside research peptides in catalogues. It is supplied here in a solid unit-dose format for research use only and is not for human or veterinary use.

Tesofensine came out of a programme at NeuroSearch A/S in Ballerup, Denmark, under the internal designation NS-2330. Thatte profiled it in 2001, the earliest compound-level account in the indexed literature (PubMed 11763162).

The preclinical record was built on transporter pharmacology. Larsen and colleagues measured hippocampal gene expression and cell proliferation in rats (PubMed 17112503). Lehr and colleagues characterised the pharmacokinetics of parent and metabolite in mice, using radioligand displacement at the dopamine transporter as the readout, and reported half-maximal concentrations for M1 four to five times higher than for tesofensine (PubMed 17982477). Li and colleagues later determined cryo-electron microscopy structures of the dopamine transporter bound to five triple reuptake inhibitors, tesofensine included (PubMed 41392177).

The transporter-level and animal record is reasonably developed and the structural work recent. This page is limited to that material, and nothing here describes an outcome in a person. Every reference was checked against PubMed retraction records.

Published work describes tesofensine as an inhibitor of presynaptic reuptake at three carriers: the dopamine transporter DAT (SLC6A3), the noradrenaline transporter NET (SLC6A2) and the serotonin transporter SERT (SLC6A4). These are sodium- and chloride-coupled members of the SLC6 family, and blocking substrate translocation slows clearance of the monoamine from the extracellular space in the preparations studied. Cryo-electron microscopy reports that tesofensine stabilises DAT in an outward-facing conformation (PubMed 41392177).

Two distinctions are useful. A reuptake blocker is not a releasing agent: substrate-type compounds are carried by the transporter and reverse its flux, while a blocker occupies the site and stops transport, so the two read differently in an assay. The metabolite M1 also contributes to activity in animal work, so parent-only readings are incomplete (PubMed 17982477).

A methodology caveat applies. Potency figures come from radioligand binding and uptake assays in transfected cells and rodent tissue, transporter pharmacology differs by species, and values belong to the assay.

Sealed tesofensine reference material is stored cool, dry and shielded from light, with -20°C conventional for long-term holding of small-molecule standards. No duration is asserted here: the stability window is on the batch Certificate of Analysis.

Small molecules of this type are generally less thermolabile than peptides, but the citrate salt is hygroscopic, meaning it takes up atmospheric moisture, which affects weighed accuracy. Capsules are stored as their label directs.

Reconstitution is the term for returning a solid compound to solution; this page defines it and gives no procedure. Tesofensine sits in the small-molecule solubility class, with limited aqueous solubility as the free base and DMSO the general in vitro solvent.

Solid material is handled in low humidity with minimal open-container exposure, and the salt form sets how much of a weighed mass is compound. Preparation parameters belong to the cited methodology and lot COA.

Identity and purity here are established by high-performance liquid chromatography with ultraviolet detection, liquid chromatography with mass spectrometry and, where required, nuclear magnetic resonance. The primary check is a mass consistent with 328.3 g/mol for the free base or 520.4 for the citrate.

Two checks are specific here. Stereochemistry carries the identity: the molecule has four defined centres, and diastereomeric impurities are a realistic synthesis outcome, so chiral analysis separates them. Salt form matters when reconciling a stated strength, since free base and citrate differ by about 192 g/mol. Novelle Bio material is batch tested with a published COA documenting verified purity.

Tesofensine is one of several non-peptide research chemicals catalogued alongside peptides.

• MK-677.
  A non-peptide receptor agonist, the closest catalogue parallel.
• 5-Amino-1MQ.
  A small-molecule enzyme inhibitor, another non-peptide entry.
• BAM15.
  A small-molecule mitochondrial uncoupler acting on a membrane.
• Dihexa.
  A small molecule built from a peptide starting point.
• SLU-PP-332.
  A synthetic nuclear receptor agonist, a third mechanism.

Thatte U (2001). NS-2330 (Neurosearch). Curr Opin Investig Drugs.
PubMed 11763162

Larsen MH, Rosenbrock H, Sams-Dodd F, et al. (2007). Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine. Eur J Pharmacol.
PubMed 17112503

Lehr T, Staab A, Tillmann C, et al. (2008). Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol.
PubMed 17982477

Li Y, Meng Y, Li N, et al. (2025). Structural basis for pharmacotherapeutic action of triple reuptake inhibitors. Nat Commun.
PubMed 41392177

Peptides.com lists one tesofensine research product, a solid unit-dose format from the house brand Novelle Bio at a listed 500mcg strength in a 60 count bottle. Those figures are product specifications, not research quantities, and there is no vial or spray listing. Tesofensine is new to the catalogue with no chemical information page, so identity figures come from PubChem.

• Browse all tesofensine research products

• Novelle Bio Tesofensine Capsules, 500mcg, 60 count

These products are sold for Research Use Only and are not intended for human consumption.