Section 1 of 8Overview
Overview
Tesofensine (NS2330) is a synthetic monoamine-reuptake inhibitor investigated for obesity and earlier neurological programmes. Human efficacy signals exist, but the evidence is not equivalent to an approved medicine. The principal 2008 obesity publication later received an expression of concern.
Investigational, not approved
An orphan-drug designation for tesofensine plus metoprolol is not FDA marketing approval; FDA’s own record says the combination is not approved for that orphan indication.
Section 2 of 8Identity and chemistry
Identity and chemistry
| Property | Verified value |
|---|---|
| PubChem CID | 11370864 |
| Molecular formula | C17H23Cl2NO |
| Molecular weight | 328.3 g/mol |
| CAS number | 195875-84-4 |
These values describe tesofensine free base. Tesofensine citrate is a separate salt record with different formula and mass and must not be mixed into this identity.
Section 3 of 8Mechanism
Mechanism
Tesofensine inhibits presynaptic reuptake of noradrenaline, dopamine and serotonin. That pharmacology can influence appetite and autonomic variables, but a plausible mechanism does not establish a favourable clinical risk–benefit balance.
Section 4 of 8Phase 2 monotherapy evidence
Phase 2 monotherapy evidence
NCT00394667 randomised 203 adults with obesity to placebo or three once-daily tesofensine doses alongside an energy-restricted diet for 24 weeks. The publication reported greater mean weight loss than placebo and 161 participants completed the study. Common adverse effects included dry mouth, nausea, constipation, diarrhoea and insomnia; heart rate increased by 7.4 beats/min in the 0.5 mg group. The publication’s later expression of concern must remain attached to any interpretation.
Section 5 of 8Combination development
Combination development
Later work has focused on Tesomet, a fixed combination of tesofensine and metoprolol. A small randomised trial in 21 adults with hypothalamic obesity reported weight-loss signals and included anxiety, sleep disturbance, dry mouth and headache among safety findings. NCT05147415 studies several Tesomet doses. Evidence for the combination does not automatically validate tesofensine monotherapy.
Section 6 of 8Regulatory context
Regulatory context
FDA granted orphan designation in 2021 to the fixed tesofensine–metoprolol combination for hypothalamic obesity. The same FDA record explicitly states that it is not FDA-approved for the orphan indication. Designation supports development; it is not evidence of marketing authorisation.
Section 7 of 8Safety and dosing
Safety and dosing
The monoamine mechanism and observed heart-rate and neuropsychiatric findings make cardiovascular, psychiatric and interaction assessment central to development. Trial doses document what researchers tested; they are not an approved regimen.
No established clinical dose
This page does not convert phase 2 or combination-study doses into treatment advice.
Section 8 of 8Evidence conclusion
Evidence conclusion
Tesofensine has genuine human trial data, but the monotherapy evidence is limited, its central publication carries an integrity warning, and current development uses a combination product. Confirmation in rigorous trials and regulatory review remain necessary.