Tesofensine
[CAS# 402856-42-2]

Identification

• Name: Tesofensine
• Synonyms: (2R,3S)-3-(3,4-Dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane
• Molecular Formula: C₁₇H₂₃Cl₂NO
• Molecular Weight: 328.28
• CAS Registry Number: 402856-42-2
• SMILES: CCOC[C@@H]1[C@H](CC2CCC1N2C)C3=CC(=C(C=C3)Cl)Cl

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.539, Calc.^*
• Boiling Point: 396.6±42.0 ºC (760 mmHg), Calc.^*
• Flash Point: 193.7±27.9 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Tesofensine is a pharmacological compound that has attracted much attention for its potential in treating obesity and neurodegenerative diseases. Originally developed as an antidepressant, Tesofensine's unique properties have shown promising results in weight management and cognitive enhancement.

Tesofensine was discovered by Danish pharmaceutical company NeuroSearch in its search for treatments for neurodegenerative diseases such as Parkinson's and Alzheimer's. The compound was initially explored for its effects on neurotransmitter levels in the brain. However, in clinical trials, researchers observed significant weight loss in patients, so the focus shifted to its potential as an anti-obesity drug.

Tesofensine is classified as a triple monoamine reuptake inhibitor and has the chemical formula C17H23NO3. It inhibits the reuptake of three key neurotransmitters: dopamine, norepinephrine, and serotonin. This inhibition increases the levels of these neurotransmitters in the brain, improving mood and cognitive function while reducing appetite.

Tesofensine's mechanism of action involves simultaneous inhibition of the reuptake of dopamine, norepinephrine, and serotonin. Increased dopamine levels increase motivation and reward, which can reduce the urge to eat. Increased norepinephrine levels increase energy expenditure and fat oxidation, which can aid in weight loss. Higher serotonin levels improve mood and create a feeling of fullness, which can reduce overall food intake.

The main application of Tesofensine is in the treatment of obesity. Clinical trials have shown that Tesofensine can significantly reduce weight by suppressing appetite and increasing energy expenditure. This makes it a promising candidate for the treatment of obesity, which is associated with a number of health risks, including diabetes, cardiovascular disease, and certain cancers.

Tesofensine's ability to increase neurotransmitter levels suggests potential benefits in the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. While its main focus is currently on obesity, its cognitive-enhancing properties remain of interest. Given its initial exploration as an antidepressant, Tesofensine may also be helpful in the treatment of mood disorders. Increased levels of dopamine, norepinephrine, and serotonin can improve mood and cognition, potentially providing therapeutic benefits for depression and cognitive decline.

Clinical trials have shown that Tesofensine has promising effects, especially in weight loss. In a Phase II clinical trial, patients treated with Tesofensine experienced significant weight loss compared to those treated with a placebo. In addition, improvements in metabolic parameters, such as reduced waist circumference and improved lipid profiles, were noted. However, the development of Tesofensine has also highlighted the importance of monitoring potential side effects. Common side effects observed include increased heart rate, increased blood pressure, and insomnia. Therefore, ongoing research is essential to optimize dosing and ensure the safety and efficacy of Tesofensine for long-term use.

Tesofensine's ability to inhibit the reuptake of multiple neurotransmitters provides a comprehensive approach to weight management and mood improvement. Clinical trials have shown that Tesofensine can cause significant weight loss, providing a potential new solution for obesity treatment. Its initial development for use in neurodegenerative diseases suggests that it has additional benefits in cognitive enhancement and neuroprotection.

While Tesofensine shows great promise, it must be used with caution. Patients should be monitored for cardiovascular side effects and the drug should be used under the supervision of a healthcare professional. Appropriate dosing and patient selection are essential to minimize risks and maximize treatment effects.