Tesofensine

InvestigationalModerate Research

Also known as: NS2330 · Triple Reuptake Inhibitor

A triple monoamine reuptake inhibitor that reduces appetite and increases metabolic rate by enhancing dopamine, norepinephrine, and serotonin signaling.

Overview

Tesofensine is a novel triple monoamine reuptake inhibitor that blocks the reuptake of dopamine, norepinephrine, and serotonin, originally developed for Parkinson's and Alzheimer's disease. During clinical trials for neurological conditions, researchers noticed significant weight loss in participants, leading to its repurposing as an anti-obesity drug. In Phase 2 obesity trials, tesofensine produced dose-dependent weight loss of up to 12.8% over 24 weeks — roughly twice the efficacy of existing anti-obesity medications at the time. It works through dual mechanisms: reducing appetite via enhanced serotonin and norepinephrine signaling in the hypothalamus, and increasing resting metabolic rate via sympathetic nervous system activation.

Tesofensine has been approved in some markets and continues development for obesity treatment.

Mechanism of Action

Inhibits the reuptake of dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters. Enhanced serotonin and norepinephrine in the hypothalamus reduces appetite. Increased norepinephrine activates the sympathetic nervous system, raising metabolic rate and thermogenesis. Dopamine enhancement improves motivation and reward signaling.

Key Benefits

Significant appetite reduction
Increased resting metabolic rate
Enhanced motivation and energy
Dose-dependent weight loss
Improved mood and cognitive function
Dual mechanism (appetite + metabolism)

Potential Side Effects

Increased heart rate
Dry mouth
Insomnia
Constipation
Potential blood pressure increase
Mood changes

Common Stacks

This peptide is commonly combined with the following compounds for synergistic effects:

SemaglutideL-Carnitine5-Amino-1MQ

Known Interactions

The following interactions have been documented for Tesofensine. Always consult a healthcare professional before combining compounds.

Use Caution (1)

Both suppress appetite through different mechanisms. Combined use may cause excessive appetite suppression, nutritional deficiencies, and cardiovascular strain.

View all compound interactions

Scientific References

Quick Reference

Typical Dose

250mcg-1000mcg

Frequency

1x daily AM

Route

Oral or injectable

Half-Life

~8-9 days

Cycle Length

4-12 weeks; 5 on 2 off or daily, followed by 4-12 weeks recovery. Fasted recommended.

FDA Status

Investigational — Phase 3 trials ongoing. Approved in some markets (Mexico). Not FDA approved in the US.

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This information is for educational purposes only. Consult a qualified healthcare professional before using any peptide. Dosing information reflects commonly reported protocols and may not be appropriate for everyone.

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