Triple monoamine reuptake inhibitor · Also known as NS-2330
An oral weight loss compound that works by inhibiting the reuptake of serotonin, norepinephrine, and dopamine, leading to reduced appetite and increased metabolic rate. Originally developed for neurological disorders, it was repurposed for obesity after patients in early trials showed significant weight loss.
Tesofensine was initially studied for Alzheimer's and Parkinson's disease by NeuroSearch, but those programs were discontinued. When phase 2 obesity trials showed approximately double the weight loss of existing medications at the time, development shifted to weight management. Saniona licensed the compound, and its partner Medix completed a phase 3 program, though regulatory approval in Mexico has been delayed.
Tesofensine blocks the reuptake transporters for three key neurotransmitters: serotonin, norepinephrine, and dopamine. By preventing these molecules from being recycled back into nerve terminals, it increases their concentrations in the synaptic cleft. This triple mechanism suppresses appetite through serotonin and norepinephrine pathways while the dopamine component may reduce food-seeking behavior and improve motivation.
Unlike injectable GLP-1 agonists that work primarily through gut-brain hormonal signaling, tesofensine acts directly on central nervous system neurotransmitter circuits. It also appears to increase resting metabolic rate, contributing to an energy deficit from both reduced intake and increased expenditure. However, the same norepinephrine effects that boost metabolism can also increase heart rate and blood pressure, which is the primary safety concern.
0.25 mg/day
Initial assessment period0.5 mg/day
24 weeks (phase 2 trial duration)Most side effects tend to improve as your body adjusts.