What Is Tesofensine?
Tesofensine is a presynaptic triple monoamine reuptake inhibitor — blocking reuptake of dopamine, serotonin, and norepinephrine simultaneously — originally developed for Parkinson's disease before its profound weight-loss effects were discovered in clinical trials. It produces among the largest weight losses documented for any oral anti-obesity agent in Phase 2 trials.
Mechanism of Action
By inhibiting reuptake of dopamine, serotonin, and norepinephrine, Tesofensine increases the synaptic availability of all three monoamines simultaneously. The weight-loss effects are mediated primarily through central mechanisms: appetite suppression via hypothalamic monoamine signaling, activation of reward circuits in ways that reduce food-seeking behavior, and modulation of the melanocortin system that regulates energy balance.
Obesity Clinical Data
The TIPO Phase 2 trial demonstrated dose-dependent weight loss: 6.5% at 0.25mg, 11.3% at 0.5mg, and 12.8% at 1mg over 24 weeks — versus 2.2% placebo. These results rank among the most significant for any oral weight-loss agent. Phase 3 trials are underway with particular focus on cardiovascular safety, given the monoaminergic mechanism. Tesofensine's original Parkinson's indication reflected its dopaminergic reuptake inhibition, which contributes to its unique appetite-modulating profile.
Quick Reference
Member reference tables summarize the compound's research parameters.
Research Indications
Research Protocols
As reported in cited literature and research-community logs (see Research Citations below), not a personal dosing recommendation.
This member section describes parameters reported in the research literature.
Peptide Interactions
This member section summarizes reported compound interactions and evidence limitations.
Reported Research Time Points
This member section summarizes reported research time points.
Safety Notes
Included for harm-reduction awareness only, in the event this compound is encountered outside its labeled research use. Inclusion here does not imply RUO Codes endorses, recommends, or instructs human use.
This member section discusses research safety considerations and uncertainties.
Quality Indicators
Research Citations
- TIPO-1 Phase IIB Trial (2008)
203 participants | 0.25-1.0mg daily | 24 weeks | Up to 10.6% weight loss - TIPO-4 Extension Trial (48 weeks)
140 participants | 0.5-1.0mg daily | 48 weeks | 13-14kg total weight loss - Viking Phase 3 Trial (2018)
372 participants | 0.25-0.5mg daily | 24 weeks | Significant weight loss - GABAergic Hypothalamic Mechanism Study (2024)
Animal model | Various doses | Acute/chronic | Neuronal activity - Appetite Suppression Mechanism Study
Rat model | 2mg/kg | 14 days | Alpha-1 and D1 receptor pathways - Centrally Acting Agents for Obesity: Past, Present, and Future
Coulter AA, Rebello CJ, Greenway FL, 2018, Drugs