Tesofensine

Human clinical Weight Loss & Metabolism 2 sources

Tesofensine is a triple monoamine reuptake inhibitor (serotonin, noradrenaline, and dopamine) originally developed for neurodegenerative diseases. Clinical trials have demonstrated its significant weight loss properties by suppressing appetite and increasing resting energy expenditure.

01Dosing reference

Amount

0.25 mg to 0.5 mg per day (oral)

Frequency

Once daily

Cycle

Continuous daily use in clinical trial settings (e.g., 24 weeks)

Reference figures, not a recommendationThese values reflect amounts described in the literature and vendor documentation this database indexes. Use the reconstitution calculator to convert them into syringe units.

02Mechanism of action

Triple Monoamine Reuptake Inhibition

Blocks the reuptake of serotonin, noradrenaline, and dopamine in the synaptic cleft.

Appetite Suppression and Energy Expenditure

Increased neurotransmitter levels in the brain reduce hunger signals and boost resting metabolic rate.

Weight Loss and Metabolic Improvement

Leads to significant reductions in body weight and improvements in metabolic markers like insulin sensitivity.

03Human evidence

Significant dose-dependent weight loss over 24 weeks.

Phase 2 clinical trial in obese patients showed weight loss of up to 10.6% compared to 2.0% for placebo.

Improvements in metabolic parameters.

Reductions in waist circumference, triglycerides, and insulin levels observed in human trials.

04Preclinical evidence

Reversal of diet-induced obesity.

Rat models showed significant weight loss and reduced food intake.

Modulation of brain reward pathways.

Animal studies indicate tesofensine affects dopamine signaling, potentially reducing cravings for high-fat foods.

05What is known vs. unknown

Reasonably established

Acts as a serotonin-noradrenaline-dopamine reuptake inhibitor (SNDRI).
Demonstrated significant weight loss in Phase 2 clinical trials.
Increases resting energy expenditure and suppresses appetite.
Originally investigated for Parkinson's and Alzheimer's diseases.

Unknowns & limits

Long-term cardiovascular safety remains a concern due to increased heart rate observed in some trials.
Phase 3 clinical trial data is limited, delaying widespread regulatory approval.

06Safety & regulatory context

Regulatory statusTesofensine has shown side effects such as dry mouth, insomnia, constipation, and dose-dependent increases in heart rate and blood pressure. Due to these cardiovascular effects, its development path has been cautious. It is not FDA-approved for weight loss or any other indication and remains an investigational compound.

07Compared with Sibutramine

Tesofensine vs. Sibutramine

Key difference

Tesofensine is a triple reuptake inhibitor (including dopamine), whereas sibutramine primarily inhibits serotonin and noradrenaline reuptake.

When researchers discuss each

Sibutramine is discussed historically as a withdrawn weight-loss drug due to cardiovascular risks, while tesofensine is discussed as a potentially more effective alternative currently under investigation.

08Glossary

SNDRI

Serotonin-noradrenaline-dopamine reuptake inhibitor, a class of drugs that block the reabsorption of these three neurotransmitters.

Resting Energy Expenditure (REE)

The amount of calories the body burns while at rest.

Synaptic Cleft

The space between neurons where neurotransmitters are released and bind to receptors.

09Knowledge check

Q1What is the primary mechanism of action of tesofensine?

Q2What was the original intended medical use for tesofensine before its weight loss properties were discovered?

Q3Which statement best reflects a documented limitation in the clinical evidence for tesofensine?

Q4Compared with sibutramine, what key pharmacological difference for tesofensine is stated in the dossier?

Q5Which safety or regulatory fact about tesofensine is supported by the dossier?

10Sources

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Research and educational use onlyNothing on this site is medical advice, a prescription, or a recommendation for human use. Compounds documented here are research chemicals. Consult a qualified clinician before making any health decision.