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Tesofensine is a synthetic small-molecule compound that inhibits the reuptake of dopamine, norepinephrine, and serotonin, thereby modulating monoaminergic signaling and appetite-related pathways.
Tesofensine, which is also called NS-2330, is a synthetic small-molecule belonging to the group of compounds related to phenyltropanes. Unlike a number of the substances listed together with peptides, tesofensine is not a peptide and so it lacks an amino-acid sequence or peptide-bond structure.
From a molecular pharmacology perspective, Tesofensine has been investigated as an inhibitor of the dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT). These membrane proteins normally participate in the transport of their respective monoamines from the extracellular environment back into cells. Laboratory studies have therefore used Tesofensine as a defined compound for investigating monoamine transporter activity, transporter inhibition and associated neurochemical signaling processes.
Experimental research has also examined the relationship between Tesofensine and its principal N-dealkylated metabolite, M1 (NS-2360). Comparative studies have investigated the activity of the parent compound and M1 at monoamine transporters, including their interaction with the dopamine transporter.
For use as a research material, Tesofensine should be described on the basis of its defined chemical identity, stereochemistry, molecular formula, molecular mass and analytical purity. Your batch certificate of analysis states that the material supplied is Tesofensine having the molecular formula C₁₇H₂₃Cl₂NO and a molecular weight of 328.28 g/mol; it also includes results from identity tests by ¹H NMR and chromatographic purity determined by HPLC.
Tesofensine is a synthetic small-molecule compound, rather than a peptide. Structurally, it contains a substituted 8-azabicyclo[3.2.1]octane framework with a 3,4-dichlorophenyl group, an ethoxymethyl substituent and an N-methyl group. The molecule contains four defined stereocentres, making its stereochemical configuration an important part of its chemical identity. The FDA substance record describes its stereochemistry as absolute, with all four stereocentres defined.
The molecular formula C₁₇H₂₃Cl₂NO and molecular weight of 328.28 g/mol for Tesofensine, as stated in the batch COA, are identical to those listed in the FDA substance record.
Unlike peptide-based research materials, Tesofensine contains no amino-acid sequence or peptide bonds. Its molecular characterization is therefore based on parameters such as chemical structure, elemental composition, stereochemistry and molecular mass rather than primary peptide sequence.
Other salt forms of Tesofensine have also been recorded, for example, the citrate and tartrate forms, these having molecular compositions different from that of the original compound. When carrying out laboratory documentation, the molecular specifications should therefore match precisely those identified by the batch-specific analytical documentation.
Tesofensine (NS-2330) has been investigated primarily through its interaction with the monoamine transporters responsible for dopamine, norepinephrine and serotonin transport. Rather than acting as a peptide–receptor ligand, Tesofensine is a small molecule that interacts with membrane transporter proteins, making transporter binding and inhibition central areas of its molecular investigation.
Monoamine Transporter Inhibition
Experimental studies have shown that Tesofensine acts as an inhibitor of the dopamine transporter (DAT), the norepinephrine transporter (NET) and the serotonin transporter (SERT); these proteins are normally responsible for transporting their respective monoamines across the cell membrane. In experiments using synaptosomes from rat brains, Tesofensine inhibited the uptake of norepinephrine, dopamine and serotonin, thus providing measurable in-vitro indicators for the characterization of its transporter activity.
Transporter-Binding Interactions
More recent structural studies have looked directly at Tesofensine in complex with the human monoamine transporters. Cryo-electron microscopy investigations have been carried out on Tesofensine bound to DAT, NET and SERT, enabling the researchers to examine the molecular interactions involved in transporter recognition and inhibition. The structural models thus offer additional insight into the way in which a single small molecule can interact with several related transporter proteins.
Dopamine Transporter Research
DAT has been looked at in rather great detail. In experimental studies, radioligand methods have been employed in order to measure the degree of DAT inhibition and occupancy, and in comparative research, Tesofensine has been studied together with its main N-dealkylated metabolite, M1 (NS-2360). The parent compound and the metabolite show different transporter-associated activity, which is why they are useful in comparative molecular pharmacology studies.
Overall, Tesofensine provides a defined small molecule for investigating monoamine transporter binding, transporter inhibition, structure–activity relationships and parent compound–metabolite interactions. These mechanisms should be described as molecular and laboratory research findings rather than being extrapolated into therapeutic effects, dosing recommendations or human-use claims.
This summary reflects findings reported in published preclinical and in vitro research. The original studies supporting this information are listed in the references.
Tesofensine has been studied in laboratory experiments using the dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters. In vitro experiments carried out on synaptosomes have measured the inhibition of monoamine uptake, thus providing quantitative measures for comparing the way in which Tesofensine interacts with the three transporter systems.
Structural studies have looked at the direct interaction between Tesofensine and the human monoamine transporters. Using cryo-electron microscopy (cryo-EM), the structure of Tesofensine in complex with DAT, NET and SERT has been determined, which has enabled the researchers to examine its binding orientation and the amino acid residues taking part in molecular recognition.
DAT offers a well-characterized experimental system for the study of Tesofensine, with radioligand-binding techniques having been employed to quantify transporter inhibition and structural and mutagenesis experiments having been used to examine the individual DAT residues that are involved in Tesofensine binding.
Structural studies of transporter recognition have looked at the tropane ring, the dichlorophenyl group and the ethoxymethyl substituent of tesofensine. Recent cryo-EM research shows that the tropane and dichlorophenyl areas form conserved interactions in the central binding cavities of DAT, NET and SERT, while the ethoxymethyl group shows greater conformational variation.
Experimental studies have compared Tesofensine with its principal N-dealkylated metabolite M1 (NS-2360). Mouse models using radiolabelled transporter ligands have investigated differences between the parent compound and M1 in relation to DAT inhibition and concentration–response characteristics.
Since DAT, NET and SERT are members of the related monoamine transporter family, tesofensine offers a well-defined small molecule which can be used for comparing the structure of the binding site and the inhibition of the transporters among these proteins. Comparative studies have revealed both conserved interactions and differences that are specific to each transporter, thus providing a molecular basis for further laboratory research.
The analytical verification of Tesofensine should involve checking that its chemical identity and purity conform to the specifications given for the material provided. Proton nuclear magnetic resonance (¹H NMR) can be used to determine whether the spectral features observed are in agreement with those expected for the molecular structure; independent Tesofensine certificates also employ ¹H NMR for structural identification.
High-performance liquid chromatography (HPLC) is capable of being used to examine the chromatographic purity by separating the main Tesofensine component from any detectable related substances or impurities. In order to obtain further confirmation of identity, LC-MS or LC-MS/MS can give molecular-mass data together with the chromatographic separation; analytical research that has already been published has employed HPLC coupled with tandem mass spectrometry in order to measure both Tesofensine and its related M1 compound.
Analytical results should be interpreted against the specification for the exact chemical form and batch supplied. The batch-specific Certificate of Analysis should therefore be reviewed alongside the relevant chromatographic and structural identification data.
Store Tesofensine research material at 2–8°C in accordance with the batch-specific Certificate of Analysis (COA). Keep the material in its original, tightly closed container in a cool, dry, well-ventilated area. Follow the current manufacturer’s documentation for any specific storage or transport requirements.
Handle the material with appropriate laboratory precautions to limit unnecessary exposure. Wear suitable gloves, protective clothing and eye protection. Avoid procedures that may generate dust or aerosols, and use adequate laboratory ventilation during handling.
Storage requirements may vary based on the material’s chemical form, physical state and batch specifications. The conditions listed on the current COA should take precedence over general storage recommendations.
Tesofensine is a synthetic small-molecule, not a peptide; it has no amino acid sequence or peptide-bond structure and is rather defined by its specific chemical structure, molecular composition, and stereochemistry.
Tesofensine contains a tropane-type bicyclic ring system, together with a dichlorophenyl group and an ethoxymethyl group. Structural research has examined how these regions of the molecule interact with monoamine transporter binding sites.
Tesofensine contains four defined stereocentres, meaning the spatial arrangement of its atoms forms part of its chemical identity. The FDA substance record identifies its stereochemistry as absolute, with all four stereocentres defined.
Laboratory research has investigated Tesofensine in relation to the dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT). These closely related membrane proteins provide experimental systems for studying transporter binding and inhibition.
Cryo-EM studies have shown Tesofensine in the central binding cavity of human DAT. The compound interacts with amino acids situated in several transmembrane regions and stabilizes an outward-facing transporter conformation, thus providing structural information regarding how it is bound.
Methods such as ¹H NMR and HPLC can provide complementary information about Tesofensine identity and purity. Your batch COA specifically uses ¹H NMR for identification and HPLC for purity assessment, so these are particularly appropriate methods to reference on the product page.
Proton nuclear magnetic resonance (¹H NMR) produces a spectrum reflecting the hydrogen environments within a molecule. Comparing the observed spectrum with the expected structural characteristics can therefore provide evidence supporting the identity of Tesofensine.
Batch-specific verification provides analytical information about the particular material being supplied, rather than relying solely on the compound's general chemical identity. The Certificate of Analysis and supporting analytical data should therefore be reviewed when assessing the stated identity and purity of each batch.
Tesofensine is supplied exclusively as a laboratory research material. The information presented on this page summarizes the scientific identity of Tesofensine and references published literature describing areas of laboratory investigation. This information is provided for scientific and educational purposes only and does not make therapeutic, medicinal, or diagnostic claims regarding this compound. This product is not intended for human or veterinary use.
