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Tesofensine
Tesofensine is a centrally acting serotonin-noradrenaline-dopamine reuptake inhibitor (SNDRI) originally developed for neurodegenerative conditions. It has gained research interest for its powerful appetite-suppressing and fat-burning effects, showing greater weight loss potential than many other agents currently studied. Unlike stimulants, Tesofensine works by regulating neurotransmitters that influence appetite and metabolism, without directly stimulating the heart.
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What is Tesofensine?
Tesofensine is a triple monoamine reuptake inhibitor (SNDRI) originally developed for neurodegenerative conditions like Parkinson's and Alzheimer's disease. It works by increasing dopamine, serotonin, and norepinephrine levels in the brain. During early trials, it was unexpectedly found to produce significant appetite suppression and weight loss, leading to its development as a powerful anti-obesity agent.
Potential Benefits Shown in Studies
- Significant appetite suppression
- Accelerated fat loss and weight reduction
- Increased energy expenditure and metabolism
- Preservation of lean body mass during dieting
- Improved mood, focus, and motivation
- No major increase in heart rate or blood pressure in clinical trials
Mechanisms of Action
Tesofensine promotes weight loss by:
- Suppressing appetite via elevated dopamine, serotonin, and norepinephrine
- Boosting energy expenditure and metabolism
- Improving mood and motivation, reducing emotional eating
- Enhancing fat oxidation and preserving lean body mass
- Avoiding stimulant-like side effects common to traditional weight-loss drugs
It is structurally similar to reuptake inhibitors used in antidepressants but exerts a unique central appetite-suppressing effect.
Molecular Structure of Tesofensine
Sequence
(6R)-1,2,3,4,6,7-Hexahydro-1-(2-methylphenyl)-6-(phenylmethyl)-3-(1-naphthalenylmethyl)-2,7-naphthyridine
Molecular Properties
Tesofensine Research Highlights
Tesofensine suppresses appetite and increases energy expenditure by inhibiting the reuptake of dopamine, norepinephrine, and serotonin, thereby enhancing signaling in brain regions that regulate hunger, mood, and metabolism.
Source: Wikipedia Overview
In a 24-week, randomized, placebo-controlled study, obese participants lost significantly more weight on Tesofensine (9.2% on 0.5 mg and 10.6% on 1.0 mg) compared to only 2.2% in the placebo group—nearly double the effect of existing obesity medications of that era.
Source: The Lancet
In the TIPO‑1 trial, the 0.5 mg dose showed meaningful reductions in body fat and waist size, along with preservation of lean mass—even as heart rate modestly increased and blood pressure remained stable.
Source: ResearchGate Clinical Summary
Additional research has linked Tesofensine to improved glucose tolerance, reduced triglyceride and insulin levels, elevated BDNF expression, and potential mood-enhancing effects, suggesting broad metabolic and neurologic implications.
Source: ResearchGate
