Tesofensine
Triple Monoamine Reuptake Inhibitor | Weight Loss
Tesofensine (NS2330) is a triple monoamine reuptake inhibitor that blocks the reuptake of dopamine, norepinephrine, and serotonin. Originally developed for Parkinson's and Alzheimer's disease, it demonstrated significant weight loss effects in early trials, leading to its development as an anti-obesity agent. Phase 2 and 3 clinical trials have shown weight loss of 10-12% over 24 weeks, making it one of the more effective investigational weight loss compounds. It works primarily by suppressing appetite and increasing energy expenditure through central nervous system mechanisms.
Daily dose
0.25-0.5mg
Frequency
Once daily
Cycle length
12-24 weeks
Storage
Room temperature
Key benefits
Potent oral weight loss agent with 9-12% body weight reduction in clinical trials. Triple monoamine reuptake inhibitor offering a different mechanism than GLP-1 agonists. Once-daily dosing with long half-life for stable blood levels.
How it works
Blocks reuptake of dopamine, norepinephrine, and serotonin, increasing their levels in appetite-regulating brain regions. Silences GABAergic feeding neurons in the hypothalamus. May also increase resting energy expenditure through noradrenergic stimulation.
Dosage protocols
Goal
Weight Loss
Dose
0.5mg · Once daily
Route
Oral
Goal
Starting Dose
Dose
0.25mg · Once daily
Route
Oral
Research indications
weight Loss
metabolic
Administration
Interactions
Safety notes
NOT FDA approved - investigational compound
Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants
May modestly increase heart rate and blood pressure
Not for those with cardiovascular disease or uncontrolled hypertension
Can cause insomnia - morning dosing only
Long half-life (~9 days) means prolonged effects and side effects
Regular cardiovascular monitoring recommended
Research studies
TIPO-1 Phase IIB Trial (2008)
203 participants | 0.25-1.0mg daily | 24 weeks | Up to 10.6% weight loss
Landmark randomized, double-blind, placebo-controlled trial demonstrating dose-dependent weight loss. The 0.5mg dose showed 9.2% weight loss, approximately double that of FDA-approved obesity medications at the time.
View study →TIPO-4 Extension Trial (48 weeks)
140 participants | 0.5-1.0mg daily | 48 weeks | 13-14kg total weight loss
Open-label extension study showing sustained weight loss over 48 weeks of treatment, with participants maintaining 13-14kg weight reduction.
Viking Phase 3 Trial (2018)
372 participants | 0.25-0.5mg daily | 24 weeks | Significant weight loss
Phase 3 registration trial meeting primary and secondary endpoints. Demonstrated significant reductions in waist circumference, body fat, visceral fat, triglycerides, and insulin levels.
View study →GABAergic Hypothalamic Mechanism Study (2024)
Animal model | Various doses | Acute/chronic | Neuronal activity
Recent study revealing tesofensine silences GABAergic neurons in the lateral hypothalamus, providing mechanistic insight into its appetite-suppressing effects. Found synergy with 5-HTP for sustained weight loss.
View study →Appetite Suppression Mechanism Study
Rat model | 2mg/kg | 14 days | Alpha-1 and D1 receptor pathways
Demonstrated that tesofensine induces appetite suppression through indirect stimulation of alpha-1 adrenoceptor and dopamine D1 receptor pathways in diet-induced obese rats.
View study →