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Tesofensine

Phase 2/3 Clinical Trials
capsuleOral

Originally developed for Parkinson's and Alzheimer's, researchers discovered it causes major weight loss as a side effect. It works by boosting three brain chemicals at once -- serotonin, dopamine, and norepinephrine -- which crushes appetite and revs up metabolism.

What to Expect

1

Week 1–2

Appetite suppression noticeable within days. Increased energy and motivation. Possible mild stimulant effects — heart rate may increase slightly.

2

Week 3–6

Significant weight loss (triple monoamine reuptake inhibition driving appetite suppression and thermogenesis). Improved mood and motivation from dopamine effects.

3

Week 8+

Substantial weight loss (10%+ body weight in trials). Sustained appetite control. Cardiovascular parameters need ongoing monitoring.

Common Side Effects

Increased heart rateElevated blood pressureDry mouthInsomniaConstipationNauseaAnxiety/restlessness
Tolerance: Possible mild tolerance to appetite suppression after 12-16 weeks
Cycling: Still in clinical trials. 12-24 week courses with cardiovascular monitoring. Requires medical supervision.

Scientific Overview

Tesofensine is a triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for Alzheimer's and Parkinson's disease. Phase 2 obesity trials demonstrated dose-dependent weight loss of 4.5–10.6% over 24 weeks through central appetite suppression and increased thermogenesis. The dopamine reuptake inhibition component differentiates it from SSRIs/SNRIs by enhancing motivation and reducing food-seeking behavior. Cardiovascular monitoring is required due to modest increases in heart rate (2–8 bpm) and blood pressure.

Dosing

0.25-0.5 mg by mouth daily. Start at the lower dose. Cycle for 12-24 weeks.

Practical Guide

Storage

Store capsules at room temperature away from moisture. Oral medication — no reconstitution needed.

Timing

Morning dosing to avoid insomnia. Do not take in the evening. Consistent daily timing.

Food

Can be taken with or without food. Food may reduce nausea.

Benefit Profile

🔥 Fat Loss
9/10
🧠 Brain & Cognition
4/10
😌 Mood & Anxiety
3/10

Medical Considerations

Medical oversight requiredNot safe during pregnancy

Contraindications

  • Uncontrolled hypertension
  • Cardiovascular disease
  • History of stroke
  • Pregnancy/nursing
  • Glaucoma
  • Concurrent MAO inhibitor use
  • Hyperthyroidism

Drug Interactions

MAO inhibitors (serotonin syndrome risk — contraindicated)SSRIs/SNRIs (serotonin syndrome risk)Stimulants (additive cardiovascular effects)Decongestants (pseudoephedrine — additive hypertension)Tramadol (seizure risk)

Recommended Monitoring

  • Heart rate and blood pressure at every visit
  • ECG at baseline and periodically
  • Psychiatric evaluation (anxiety, mood changes)
  • Weight and body composition

This information is for educational purposes only. Always consult a qualified healthcare provider before starting any peptide protocol.

Pricing

VendorVariantPrice
Swiss Chems
FDA warning letter received late 2024
60ct 0.25mg$69.95BEST
Peptide Sciences
Announced voluntary shutdown
30ct 0.5mg$79.00

Published Research

20 studies indexed(2007–2018)1 meta-analysis9 clinical trials10 reviews

Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease.

Astrup A, Meier DH, et al.·Obesity (Silver Spring)·2008
Meta-Analysis

The effect of tesofensine on appetite sensations.

Gilbert JA, Gasteyger C, et al.·Obesity (Silver Spring)·2012
Clinical Trial

Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users.

Schoedel KA, Meier D, et al.·Clin Pharmacol Ther·2010
Clinical Trial

Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine.

Lehr T, Staab A, et al.·AAPS J·2010
Clinical Trial

The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men.

Sjödin A, Gasteyger C, et al.·Int J Obes (Lond)·2010
Clinical Trial

A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam.

Lehr T, Staab A, et al.·Clin Pharmacokinet·2009
Clinical Trial

Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.

Rascol O, Poewe W, et al.·Arch Neurol·2008
Clinical Trial

Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial.

Astrup A, Madsbad S, et al.·Lancet·2008
Clinical Trial

Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease.

Lehr T, Staab A, et al.·Br J Clin Pharmacol·2007
Clinical Trial

Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease.

Hauser RA, Salin L, et al.·Mov Disord·2007
Clinical Trial
Showing 10 of 20 studies. Search PubMed for the complete list.

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