Tesofensine

Tesofensine is an SNDRI that modulates dopamine, serotonin, and norepinephrine to suppress appetite, enhance metabolism, and elevate mood. Initially tested for Parkinson’s and Alzheimer’s; now studied for obesity.

- Suppress appetite and improve metabolism

- Support mood, focus, and energy

Mechanism of Action

How this peptide works in the body

Neurotransmitter Reuptake Inhibition:

Tesofensine inhibits serotonin (SERT), norepinephrine (NET), and dopamine (DAT) transporters, preventing reuptake and increasing synaptic concentrations of these neurotransmitters. This enhances neurotransmission in the hypothalamus, limbic system, and prefrontal cortex, modulating appetite, mood, and reward-based behaviors.

Serotonin-Mediated Satiety:

Elevated serotonin (5-HT) levels activate 5-HT2C receptors in the hypothalamic arcuate nucleus, stimulating pro-opiomelanocortin (POMC) neurons while inhibiting neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons. This suppresses hunger signals, prolongs satiety, and reduces caloric intake.

Norepinephrine-Induced Thermogenesis:

Increased norepinephrine (NE) signaling activates β-adrenergic receptors (β3-AR) in brown adipose tissue (BAT), stimulating uncoupling protein 1 (UCP1)-mediated thermogenesis and lipolysis. This enhances basal metabolic rate (BMR) and promotes fat oxidation for energy production.

Dopamine-Driven Reward Regulation:

Elevated dopamine (DA) levels enhance signaling in the mesolimbic reward pathway (ventral tegmental area to nucleus accumbens), reducing hedonic eating and food cravings. Increased DA transmission also improves motivation, focus, and cognitive function, supporting long-term adherence to dietary changes.