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Peptide Encyclopedia / Tesofensine

Encyclopedia

Tesofensine

Tesofensine is a small-molecule triple reuptake inhibitor that blocks the reabsorption of dopamine, norepinephrine, and serotonin, and it is not a peptide. Developers first pursued it for neurodegenerative disease, then shifted to obesity after weight loss showed up as a side effect. It has cleared Phase 2 trials and entered a Phase 3 program, but it is not FDA-approved in the US. Below you'll find reported dosing, safety, and legal status. Educational only, not medical advice.

Start free →Dose tools
CategoryGLP-1 / Metabolic
Regulatory statusNot FDA-approved in the US (investigational).

Mechanism

A small-molecule triple monoamine reuptake inhibitor (blocks reuptake of dopamine, norepinephrine, and serotonin) -- NOT a peptide. Originally developed for neurodegenerative disease; weight loss was observed as a side effect, redirecting it toward obesity.

Half-life

Long; reported on the order of ~8 days (~200 hours) in humans, consistent with once-daily oral dosing. It is a small molecule, not a peptide.

Regulatory status

Not FDA-approved in the US (investigational). Has progressed through Phase 2 trials and an FDA-endorsed Phase 3 program; rights held by Saniona historically. Not a marketed US drug.

Safety

Reported dose-dependent increases in heart rate and blood pressure, plus dry mouth, insomnia, nausea, and mood-related effects consistent with monoaminergic stimulants. Cardiovascular caution.

Evidence

Human clinical trials (Phase 2 completed; Phase 3 program); investigational.

Sources

  1. Astrup A, Madsbad S, Breum L, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients (TIPO-1). Lancet. 2008;372(9653):1906-1913. https://pubmed.ncbi.nlm.nih.gov/18950853/
  2. Astrup A, Meier DH, Mikkelsen BO, et al. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease. Obesity. 2008;16(6):1363-1369. https://pubmed.ncbi.nlm.nih.gov/18356831/
  3. Sjodin A, Gasteyger C, Nielsen AL, et al. Effect of tesofensine on energy metabolism and appetite in overweight and moderately obese men (TIPO-2). Int J Obes. 2010;34(11):1634-1643. https://pubmed.ncbi.nlm.nih.gov/20479765/
  4. Appel L, Bergstrom M, Buus Lassen J, Langstrom B. Tesofensine dopamine transporter occupancy by PET. Eur Neuropsychopharmacol. 2014;24(2):251-261. https://pubmed.ncbi.nlm.nih.gov/24239329/
  5. Axel AMD, Mikkelsen JD, Hansen HH. Tesofensine induces appetite suppression via alpha1 adrenoceptor and dopamine D1 receptor pathways. Neuropsychopharmacology. 2010;35(7):1464-1476. https://pubmed.ncbi.nlm.nih.gov/20200509/
  6. Hansen HH, Hansen G, Tang-Christensen M, et al. Tesofensine induces sustained weight loss and improves glycemic control vs sibutramine and rimonabant. Eur J Pharmacol. 2010;636(1-3):88-95. https://pubmed.ncbi.nlm.nih.gov/20385125/
  7. Perez CI, Luis-Islas J, Lopez A, et al. Tesofensine silences GABAergic hypothalamic neurons. PLOS ONE. 2024;19(4):e0300544. https://pubmed.ncbi.nlm.nih.gov/38656972/
  8. 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. https://pubmed.ncbi.nlm.nih.gov/35294397/

PepWise is an informational and educational tracking tool, not medical advice and not a medical device. Tesofensine may be experimental, restricted, or prescription-only; many research peptides are not FDA-approved. Consult a licensed healthcare provider before starting, changing, or stopping any protocol. Operated by STC Consulting, Inc.