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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
In Phase II clinical trials, participants lost an average of 10% of body weight over 24 weeks, outperforming orlistat and sibutramine.
Tesofensine promotes fat loss without significant lean mass reduction, which is ideal for patients seeking body recomposition.
By enhancing key neurotransmitters in the brain, Tesofensine strongly reduces hunger and food cravings, particularly for high-calorie or sugary foods.
Despite its powerful effects, Tesofensine has shown minimal cardiovascular side effects at moderate doses, with good tolerance in long-term trials.
