Description
Tesofensine (NS2330) is a centrally-acting inhibitor of norepinephrine, dopamine and serotonin reuptake. The substance was originally developed by NeuroSearch for treatment of Parkinson’s and Alzheimer’s; in both indications development was stopped due to insufficient efficacy. In clinical trials, however, a consistently dose-dependent weight loss emerged, leading the substance into Phase II studies for obesity treatment.
Per study reports Tesofensine produces marked appetite reduction through enhanced activation of noradrenergic and dopaminergic satiety pathways in the hypothalamus. In the Astrup 2008 study (Lancet), subjects on an energy-restricted diet lost on average 4.5% of their body weight on 0.25mg, 9.2% on 0.5mg and 10.6% on 1mg Tesofensine daily over 24 weeks, compared with 2.0% on placebo.
In Mexico Tesofensine is approved as an obesity therapeutic. In the US and Europe development was stopped due to insufficient differentiation against GLP-1 agonists - efficacy was good but the safety profile did not measure up against Semaglutide/Tirzepatide.
Pharmacokinetically orally bioavailable with a very long half-life of about 8 days. Steady-state is established after 6-8 weeks. Known effects in studies: increased heart rate, dry mouth, nausea, constipation, insomnia (especially with late dosing), mood swings.
You can order Tesofensine as oral tablets in one bottle with 500mcg per tablet.
This information is for research and educational purposes only. No medical recommendations.
Risks & Safety
Tesofensine sits in the mid range of the risk scale. As a centrally-acting triple reuptake inhibitor the compound belongs to the stimulant class. Its effects are clearly documented in the clinical studies.
Documented in studies and the literature:
- Blood pressure: in the Astrup study blood pressure did not rise significantly on 0.25 and 0.5mg, heart rate did (about 7 beats per minute more on 0.5mg).
- Tachycardia: raised heart rate is a documented accompanying effect of the monoaminergic stimulation.
- Insomnia: documented, especially with late dosing, which is linked to the very long half-life.
- Mood swings: described as an accompanying effect in the clinical studies.
- Serotonin syndrome risk: in combination with other monoamine reuptake inhibitors or MAO inhibitors the risk is documented.
Monitoring via bloodwork is recommended. This classification does not replace medical advice. Risk and responsibility for any actual use lie entirely with the buyer.
Studies
- Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial - The Lancet 2008, Astrup et al: Phase II gold-standard study on weight loss and body composition.
- Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of alpha1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat - Neuropsychopharmacology 2010, Axel et al: mechanism study on appetite suppression via alpha1 and dopamine D1 receptor pathways.
- The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men - International Journal of Obesity 2010, Sjödin et al: clinical study on energy metabolism and appetite in overweight men.
- Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats - Obesity 2013, Bentzen et al: animal study on the cardiovascular adverse effects and their modulation.
