Tesofensine is a small-molecule triple monoamine reuptake inhibitor — it blocks the transporters for norepinephrine, dopamine and serotonin — and it is not a peptide. It began life as a candidate for neurodegenerative disease and was redirected toward metabolic research after appetite-related observations emerged in those early trials. It is the only compound in our fat-loss range that acts through central monoamine pharmacology, which makes it both a distinctive research tool and the one requiring the most careful handling. We supply research-grade tesofensine as 0.5 mg capsules, for laboratory use only.
What is tesofensine, precisely
Monoamine transporters — NET, DAT and SERT — sit on presynaptic terminals and recover released neurotransmitter from the synaptic cleft. Blocking a transporter raises the concentration and prolongs the presence of its neurotransmitter in the synapse. Most clinically familiar drugs in this space are selective: SSRIs block SERT, some ADHD medications target NET and DAT. Tesofensine, cited as NS2330 in the literature, blocks all three, which is why it is described as a triple reuptake inhibitor.
Chemically it is a phenyltropane derivative — the same structural family as several transporter ligands used as pharmacological tools — with a molecular weight of 262.19 g/mol and CAS 402856-42-2. It has no relationship to any peptide, and none of the analytical, storage or reconstitution conventions of peptide work apply to it.
Origin and structure
- Compound class. Small-molecule phenyltropane, non-peptide, from a central nervous system discovery programme.
- Identifiers. CAS 402856-42-2, molecular weight 262.19 g/mol.
- Targets. Norepinephrine, dopamine and serotonin transporters, with reported potency highest at NET and DAT and somewhat lower at SERT.
- Format supplied. Oral capsules at 0.5 mg per capsule, in 30-count and 60-count bottles — not a lyophilized vial, because a stable crystalline small molecule does not require freeze-drying.
How tesofensine is thought to work
Elevated synaptic norepinephrine and dopamine in hypothalamic and mesolimbic circuits is the reported basis for the appetite and feeding-behaviour effects described in preclinical work. Norepinephrine and dopamine signalling in the arcuate nucleus and related structures modulates food intake, and dopaminergic signalling in reward circuitry influences the motivational component of feeding rather than hunger as such. Rodent studies have reported reduced food intake and changes in body composition, and some work has described effects on energy expenditure alongside intake.
Because the mechanism is central and monoaminergic rather than peripheral and metabolic, tesofensine belongs to a different experimental category from incretin agonists like semaglutide or enzyme inhibitors like 5-Amino-1MQ. It is a tool for asking questions about the neural control of feeding, and studies pairing a monoaminergic and a peripheral mechanism exist precisely because the two act on separate arms of the same system. See the brain and neuropeptide hub for the wider context.
Two features of the transporter profile shape how the compound should be used experimentally. First, the potency ranking across the three transporters is not equal, and the composite effect at any given occupancy is a weighted mixture rather than uniform blockade — so behavioural readouts obtained across a concentration range may reflect different transporter combinations at each point. Second, occupancy at monoamine transporters is slow to reverse relative to receptor binding, meaning washout in a cell or tissue preparation takes longer than intuition suggests. Designs that assume rapid reversibility, or that pool observations across a wide concentration range as though one mechanism were operating throughout, will produce results that are difficult to interpret.
What research has examined
- Transporter pharmacology. Radioligand binding and uptake inhibition assays at NET, DAT and SERT establishing the potency profile that defines the compound.
- Rodent studies. Food intake and body composition in obesity models, microdialysis measuring extracellular monoamine concentrations in specific brain regions, and behavioural work on reward and motivation.
- Human clinical trials. Phase 2 trials in obesity were conducted and reported weight outcomes; earlier trials in Parkinson disease and Alzheimer disease, the original indications, did not meet their endpoints. The metabolic programme did not lead to approval in the United States.
- Cardiovascular signals. Clinical trials reported increases in heart rate and blood pressure, a documented finding for the compound and a direct pharmacological consequence of raising synaptic norepinephrine. Our specification sheet lists this explicitly as a known safety signal.
The trial history is itself instructive for anyone weighing this compound as a research tool. A molecule that failed its original neurological indications and was redirected on the strength of a side observation carries a particular kind of evidential risk: the metabolic hypothesis was generated by the same trials that tested something else, and was never independently confirmed to approval standard. That does not make the pharmacology wrong — the transporter blockade is well characterised — but it does mean the link between transporter occupancy and any whole-organism outcome should be read as an open research question rather than an established one, and comparator arms drawn from better-validated mechanisms are worth including wherever the design allows.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Form | Oral-format capsules, 0.5 mg per capsule, sealed bottle |
| Sizes | 30 capsules, 60 capsules |
| Purity | Analytically tested; certificate of analysis available |
| CAS | 402856-42-2 |
| Molecular weight | 262.19 g/mol |
| Targets | NET, DAT, SERT (triple monoamine reuptake inhibitor) |
| Known safety signal | Heart rate and blood pressure increases reported in clinical trials |
| Storage | Room temperature, sealed, dry, protected from light |
| Intended use | Laboratory research only |
Sizes are listed on the tesofensine product page, within the fat-loss and metabolic collection and the wider research compounds range.
Handling and storage in a lab context
There is no reconstitution step. Tesofensine is supplied as a solid-format capsule, stored at room temperature, sealed, dry and protected from light — conditions entirely unlike the minus 20 degrees Celsius regime that lyophilized peptides require. Where an experiment needs the compound in solution, the capsule contents must be extracted and the excipient matrix accounted for, since capsule fill contains bulking agents that are not part of the active substance. That extraction step introduces a quantitation problem the raw powder format would not, and any laboratory planning solution work should factor it into the design.
Our specification sheet flags a handling note that belongs in bold: this is a centrally active compound requiring standard controlled-laboratory precautions. Unlike a peptide with poor oral bioavailability and no central activity, an orally active monoamine reuptake inhibitor is consequential if mishandled, and secure storage with restricted access is appropriate.
Purity, COA and how to read it
A certificate for a capsule product answers a different question from a certificate for a bulk chemical. It should confirm identity and purity of the active substance and, ideally, content uniformity — how much active substance each capsule actually contains, which for a 0.5 mg fill is the analytically demanding part. Identity by mass spectrometry and, where available, NMR is appropriate for a synthetic small molecule; HPLC purity applies to the active substance rather than to the capsule as a whole. Net peptide content has no equivalent here. See how to read a COA.
Comparability with the wider transporter literature is one genuine strength of this compound. Because monoamine transporter pharmacology is extremely well characterised, with selective reference ligands available for each transporter, a study using tesofensine can be anchored to a large body of established work in a way that is not possible for peptides with no identified receptor. Where the research question concerns the consequences of blocking several transporters at once rather than one, that established comparator set is what makes the design interpretable, and it should be built into the panel rather than added afterwards.
Regulatory status
Tesofensine is not approved as a medicine in the United States. Its development programme in obesity did not lead to US approval, and its earlier neurology programme did not meet its endpoints. Regulatory status differs in some other jurisdictions, which does not alter the status of research material sold here: it is supplied as a laboratory reference chemical, research use only, not approved or formulated for human or veterinary administration. Given its central activity and the documented cardiovascular signal, the research-use restriction on this compound is a substantive safety boundary, not a formality. See research use only, explained.
Related compounds and comparisons
Within our metabolic range the mechanistically distinct alternatives are 5-Amino-1MQ, an enzyme inhibitor, and SLU-PP-332, a transcriptional agonist — compared in 5-Amino-1MQ vs SLU-PP-332. For peripheral peptide mechanisms see the GLP-1 and incretin collection; for the wider field, the metabolic research overview.