Summary

Tesofensine is a triple monoamine reuptake inhibitor (dopamine, noradrenaline, serotonin) originally developed for Parkinson's and Alzheimer's disease, with significant weight loss demonstrated in Phase 2 obesity trials. It is not approved as a medicine in the UK and is not a peptide, though it is frequently discussed in peptide and research chemical communities.

Mechanism

Tesofensine inhibits the dopamine transporter (DAT), noradrenaline transporter (NAT), and serotonin transporter (SERT), increasing synaptic concentrations of all three monoamines. The dopaminergic and noradrenergic effects are thought to mediate appetite suppression via hypothalamic signalling, while serotonergic effects may contribute to satiety. Unlike sibutramine (which was withdrawn for cardiovascular risk), tesofensine has a more balanced monoamine profile, though cardiovascular concerns remain.

Evidence base

Evidence Grading: Moderate

Human clinical data: Phase 2 RCT (n=203) demonstrated significant weight loss at 0.5 mg and 1.0 mg doses (Astrup et al., 2008). Phase 2 trials in Parkinson's disease (n=321) showed modest symptomatic benefit.

Limitations: No Phase 3 trials completed for obesity. Cardiovascular safety signals (increased heart rate, elevated blood pressure) have slowed development. Long-term safety data is lacking. No published combination studies with incretin-based therapies.

Key gap: Phase 3 efficacy and safety data for obesity remain absent.

Protocols

In the Phase 2 obesity trial, tesofensine was administered at 0.25 mg, 0.5 mg, or 1.0 mg once daily for 24 weeks. The 0.5 mg dose is most commonly referenced in research discussions as offering the best benefit-to-risk ratio. Morning administration is recommended due to stimulant properties. No published research supports doses above 1.0 mg daily.

Tesofensine is not licensed as a medicine by the MHRA and is not a controlled substance. It exists in a UK grey area when sold explicitly as a research chemical. Marketing for human consumption would violate MHRA regulations on unlicensed medicines. Researchers should be aware that MHRA guidance on research peptides (2026) tightened labelling requirements for such compounds.

Vendor notes

Tesofensine is available from some UK-based research chemical suppliers. Researchers should verify supplier COAs and purity claims. See the vendor vetting guide for evaluation criteria.

References

  1. Astrup A, et al. Weight loss produced by tesofensine in obese adults: a randomised, double-blind, placebo-controlled trial. The Lancet. 2008;372(9653):1906-1913. doi:10.1016/S0140-6736(08)61507-5
  2. van Nieuwenhuyzen A, et al. Tesofensine treatment in Parkinson's disease: results of a phase 2 trial. Movement Disorders. 2008;23(suppl 1):S286.
  3. Sjödin P, et al. Pharmacokinetics and pharmacodynamics of tesofensine in healthy volunteers. European Journal of Clinical Pharmacology. 2019;75(2):243-251.