Tesofensine
A triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally for Parkinson's/Alzheimer's, now for weight loss.
Common Dosage
0.25mg - 0.5mg oral daily
Category
Weight Loss
- Appetite suppression
- Metabolic rate increase
- Mood enhancement
Tesofensine was originally developed by NeuroSearch as a treatment for Parkinson's disease and Alzheimer's disease due to its triple monoamine reuptake inhibition (serotonin, norepinephrine, dopamine). While it showed only modest efficacy for neurological conditions, Phase II trials revealed unexpectedly potent weight loss effects — exceeding those of any approved weight loss medication at the time. This led to its development pivot into obesity treatment. It has not yet achieved FDA approval but remains in development.
As a serotonin-norepinephrine-dopamine reuptake inhibitor, Tesofensine works primarily through appetite suppression and metabolic rate increase. The dopamine component enhances reward sensitivity and may reduce food cravings more specifically than serotonergic-only approaches. The norepinephrine component directly increases metabolic rate through sympathetic nervous system activation — contributing to energy expenditure beyond caloric restriction alone.
- Obesity and weight management
- Metabolic rate enhancement
- Appetite suppression in severe obesity
- Combination therapy with GLP-1 agonists
Phase 2b TIPO-1 Trial
The Phase 2b trial demonstrated 12.8% body weight loss at 0.5mg over 24 weeks — exceeding FDA-approved agents at the time. The appetite suppression was dramatic, with many participants reporting a near-complete loss of interest in food.
- Dry mouth, insomnia, and nausea are common
- Cardiovascular effects — increased heart rate and blood pressure from norepinephrine component; caution in hypertension
- Dopamine activity creates mild mood elevation and potential for dependency — not appropriate for those with substance use history
- Not FDA-approved; research-grade versions lack regulatory oversight
- Combination with other serotonergic compounds risks serotonin syndrome
- Dry mouth
- Insomnia
- Increased heart rate