Tesofensine 500mcg – 60 capsules

Tesofensine 500 mcg — 60 oral research capsules (preorder). Tesofensine is a triple monoamine reuptake inhibitor (serotonin / noradrenaline / dopamine) originally developed for Parkinson’s and Alzheimer’s disease, where it failed efficacy endpoints — but unexpectedly produced the largest weight-loss signal ever recorded in a Phase II obesity trial. In a 24-week placebo-controlled study, 1.0 mg daily produced 12.8 kg of weight loss versus 2.2 kg on placebo: roughly twice the magnitude observed with sibutramine, and approaching the range now seen with tirzepatide and retatrutide despite a fundamentally different mechanism. The molecule has since advanced through Phase III in hypothalamic obesity. The 500 mcg per-capsule potency corresponds to the lower clinical-pharmacology dose tier.

Research Overview

Tesofensine is a tropane derivative that inhibits the dopamine, serotonin and noradrenaline transporters with relatively balanced affinity — distinguishing it from the predominantly serotonergic profiles of older anti-obesity SNRIs [1]. The compound was originally developed by NeuroSearch as a treatment for Parkinson’s and Alzheimer’s disease; it failed primary efficacy endpoints in those indications but unexpectedly produced sustained weight loss in nearly every cohort tested. The pivotal Phase II TIPO-1 trial reported placebo-subtracted weight loss of 6.7 % at 0.5 mg, 11.3 % at 1.0 mg and 12.8 kg at 1.0 mg over 24 weeks, with appetite reduction and reductions in hunger ratings as the proximate mechanism — the magnitude approaches modern incretin therapies despite operating through an entirely different pathway [1,2]. The molecule has subsequently been combined with metoprolol (Tesomet) to mitigate cardiovascular signal, and has advanced through Phase III in hypothalamic obesity and Prader–Willi syndrome [2,3]. In experimental research, tesofensine is widely used as a clean tool to dissect appetite-suppressing versus reward-modulating effects of triple-monoamine pharmacology.

Primary Research Areas

• Appetite and food-reward research — preclinical and human evidence of central appetite suppression independent of GLP-1/GIP/leptin pathways, with reduction in hedonic food choice [1].
• Triple-monoamine reuptake-inhibitor pharmacology — the leading clinical-stage probe of balanced dopamine/noradrenaline/serotonin reuptake inhibition outside the antidepressant ATC class [1].
• Obesity and metabolic-syndrome models — Phase II and III evidence of double-digit weight loss; investigated for hypothalamic obesity, Prader–Willi, and rare genetic obesity syndromes [2,3].
• Reward, motivation and addiction research — Δ-dopaminergic enhancement makes it a useful probe of reward-circuit pharmacology and a comparator molecule in stimulant and food-addiction paradigms [1].
• Neurological / Parkinson’s disease research — the original development indication; preclinical models continue to use tesofensine as a balanced triple-monoamine reuptake tool [1].

References

1. Astrup A, Madsbad S, Breum L, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9653):2199–2207.
2. Sjödin A, Gasteyger C, Nielsen AL, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond). 2010;34(11):1634–1643.
3. Huynh K, Klose M, Krogsgaard K, et al. Randomized controlled trial of tesomet for weight loss in hypothalamic obesity. Eur J Endocrinol. 2022;186(6):687–700.