Tesofensine

Tesofensine Benefits for Overall Health

• Fights obesity [6-23]
• Improves cognitive health [24-32]
• Improves mood [33-35]
• Improves blood sugar levels [36-38]
• Increases energy levels [35, 39]
• Treats sexual dysfunction [35, 40]
• Treats eating disorders [8, 41-45]
• Treats attention-deficit/hyperactivity disorder (ADHD) [46-49]
• Improves sleep quality [50-57]
• Fights alcohol addiction [58-62]

What is Tesofensine?

Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor or also known as a triple reuptake inhibitor, which means that it inhibits the reabsorption of the neurotransmitters (brain chemicals) serotonin, norepinephrine, and dopamine. This process increases the extracellular concentrations of these neurotransmitters. The therapeutic benefits of tesofensine are attributed to this effect because each of these neurotransmitters exerts an important function at different locations in the brain.

How Tesofensine Works?

Tesofensine works by boosting the levels of brain chemicals (neurotransmitters) such as dopamine, norepinephrine, and serotonin. Dopamine is associated with the regulation of motor function, mood, motivation, reward, cognitive function, and reproductive behaviours. Norepinephrine increases the force of the contraction of the skeletal muscle and the heart to ensure optimal body function. Serotonin is responsible for the regulation of mood, memory, sleep, and appetite.

Chemical Structure of Tesofensine

Research on Tesofensine

Fights Obesity

Tesofensine is widely known as a weight loss drug. Researchers believe that tesofensine may help treat obese and overweight patients because it boosts the levels of dopamine in the brain. A deficiency in this neurotransmitter has been shown to be linked with overeating and obesity. [1-5] An overwhelming body of human studies supports the fat-burning effect of tesofensine:

1. 1. The results of the 2018 phase 3 Viking study showed that obese patients who received both doses of oral tesofensine (0.25 and 0.50 mg once daily) had statistically and clinically significant weight loss with low incidence of adverse events at week 24. [6]
   2. The results of the Phase 2b trial (TIPO-1) showed that obese patients treated with tesofensine lost an average of 12.8 kg on the 1 mg dose, 11.3 kg on the 0.5 mg dose and 6.7 kg on the 0.25 mg dose, compared with a 2.2 kg loss in the placebo group, suggesting that tesofensine has the potential to produce a weight loss twice that of currently approved drugs. [7]
   3. In the TIPO-2 trial, tesofensine administration in obese patients reduced their desire to eat and increased their satiety levels after 14 days of treatment. [8]
   4. In obese patients, tesofensine treatment at varying doses (0.25 mg, 0.5 mg or 1.0 mg) resulted in statistically significant and clinically relevant weight loss with positive effects on energy balance, appetite, physical activity, and quality of life. [9]
   5. In obese patients, tesofensine administration at a dose of 0.5 mg for 26 weeks produced weight loss twice that of anti-obesity agents such as sibutramine or rimonabant. [10]
   6. In overweight patients, tesofensine administration for 24 weeks is associated with enhanced appetite suppression and significant weight loss. [11]
   7. In phase II clinical trials with tesofensine in obese individuals, significant reductions in body weight, body fat and waist circumference were observed without any adverse side effects. [12]
   8. In obese patients, long-term tesofensine supplementation is well-tolerated and resulted in significant weight loss.[13]
   9. In patients with Parkinson’s or Alzheimer’s disease, tesofensine administration once daily for 14 weeks without any weight loss program induced weight loss of approximately 4%, which is similar to that of sibutramine. [14]
   10. In healthy males, multiple administration of tesofensine at doses of 0.125–1 mg induced a significant increase in dopamine levels, resulting in appetite suppression. [15]
   11. In the diet-induced obese rat, tesofensine administration resulted in appetite suppression and weight loss with reversal of low forebrain dopamine levels. [16-17]
   12. In a rat model of diet-induced obesity (DIO), administration of tesofensine (2.0mg/kg, s.c.) for 16 days significantly reduced body weights. [18]
   13. In diet-induced obese rats, tesofensine treatment at 2 mg/kg for 28 days decreased food intake and body weight. [19]
   14. In 203 obese persons, tesofensine 0.5 mg produced a weight loss twice that of currently approved anti-obesity drugs. [20]
   15. In obese patients, tesofensine administration resulted in a 10% average weight loss in 24 weeks. [21]
   16. A study showed that tesofensine showed a stronger weight-reducing effect than that of currently approved anti-obesity drugs. [22]
   17. In obese patients, tesofensine in combination with an energy-restricted diet effectively reduced the weight of the subjects. [23]

Improves Cognitive Health

Research indicates that tesofensine helps preserve cognitive health by indirectly potentiating cholinergic neurotransmission, which is a process wherein nerve cells relay messages to each other. [24] This has been proven to have beneficial effects on various areas of cognitive health, including learning, memory, and thinking skills. The following studies support this effect:

1. 1. The first clinical results of two small 4-week phase IIa trials performed in patients with mild Alzheimer’s disease (AD) showed that tesofensine treatment induced significant improvement in cognitive function. [25-26]
   2. A growing body of research indicates that obesity is a major risk factor for cognitive impairment, especially in the older population. [27-30] With its anti-obesity effect, tesofensine may help protect against cognitive impairment.
   3. In a mouse model of Alzheimer’s disease, tesofensine administration decreased the brain concentrations of amyloid beta, which are abnormal protein aggregates and is the causative agent of the disease. [31]
   4. In patients with advanced Parkinson’s disease and motor fluctuations, low-dose tesofensine improved activities of daily living and motor function. [32]

Improves Mood

Sustained treatment with tesofensine has been shown to improve overall mood through its antidepressant effect. Studies show that tesofensine affects mood by:

1. 1. Increasing the levels of brain-derived neurotrophic factor (BDNF), thereby triggering an antidepressant effect. [33]
   2. Triggering an anti-anxiety effect in obese patients with comorbid depression and anxiety symptoms. [34]
   3. Increasing the levels of the neurotransmitters serotonin, noradrenaline, and dopamine. [35]

Improves Blood Sugar Levels

Tesofensine has also been found to have beneficial effects on blood sugar. Studies show that:

1. 1. In obese patients, administration of tesofensine at varying doses (0.25 mg, 0.5 mg, and 1.0 mg) resulted in a significant reduction in blood sugar levels and an improvement in quality of life. [36]
   2. In rodents, tesofensine also induced a significant reduction in blood sugar levels in addition to weight loss. [37-38]

Increases Energy Levels

Tesofensine treatment is also beneficial in improving one’s productivity by increasing energy levels. Evidence supports the energy-boosting effects of tesofensine:

1. 1. A study found that tesofensine can boost energy by increasing the levels of the neurotransmitters dopamine and norepinephrine, which are responsible for regulating motivation, energy, interest, and drive. [35]
   2. In one study, the administration of tesofensine in overweight and moderately obese men induced higher energy expenditure compared to a placebo. [39]

Treats Sexual Dysfunction

Because of its potent antidepressant effect, tesofensine has also been studied for its therapeutic benefits on sexual dysfunction, according to studies:

1. 1. Tesofensine has the capacity to increase the levels of dopamine, a neurotransmitter that contributes to the desire for sexual activity, erection, and ejaculation. [35]
   2. Tesofensine administration is effective in treating depression-related sexual dysfunction, suggesting that it can help ramp up sexual power. [40]

Treats Eating Disorders

Studies reported that triple reuptake inhibitor such as tesofensine also holds therapeutic potential for eating disorders:

1. 1. In obese patients, tesofensine administration reduced their desire to eat and increased their satiety levels after 14 days of treatment. [8]
   2. In patients with binge eating disorder, a condition in which a person eats large quantities of food when stressed, tesofensine administration has been shown to improve its symptoms, possibly due to tesofensine’s potent antidepressant effect. [41-44]
   3. In the diet-induced obese rat, tesofensine induced appetite suppression by indirect stimulation of α1 adrenoceptor and dopamine d1 receptor pathways. [45]

Treats Attention-Deficit/Hyperactivity Disorder (ADHD)

ADHD is characterized by short attention span, hyperactivity and impulsivity, and is common in children and even adults. Evidence suggests that tesofensine may have beneficial effects on this mental condition:

1. 1. Studies show that ADHD is strongly linked with low levels of dopamine and serotonin and that tesofensine can have beneficial effects on this condition by increasing the levels of these neurotransmitters. [46-48]
   2. A study reported that tesofensine can lower the risk of ADHD associated with obesity. [49]

Improves Sleep Quality

Studies suggest that tesofensine’s ability to increase the levels of certain neurotransmitters can help improve sleep quality:

1. 1. A deficiency in the neurotransmitter serotonin has been linked to insomnia and various sleeping difficulties. [50-55]
   2. Studies reported that increasing the levels of serotonin through selective serotonin reuptake inhibitors treatment has been shown to improve objective and subjective sleep quality in patients with sleeping difficulties – an effect similar to tesofensine. [56-57]

Fights Alcohol Addiction

There’s also evidence suggesting that tesofensine can cure alcohol addiction via its ability to boost neurotransmitter levels:

1. 1. Studies show that low dopamine levels are associated with alcohol addiction – with tesofensine’s ability to increase dopamine levels, it may help reduce excessive alcohol intake along with its symptoms. [58-61]
   2. In ethanol-preferring rats, triple reuptake inhibitor administration reduced alcohol consumption without decreasing food or water consumption. [62]

Associated Side Effects of Tesofensine

Tesofensine side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on tesofensine. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of tesofensine. Despite this, it was listed as a side effect associated with tesofensine even though these associated side effects are very uncommon.

Side effects associated with tesofensine may include the following:

• Constipation
• Diarrhea
• Dry mouth
• Headache
• Increased blood pressure
• Increased heart rate
• Insomnia
• Nausea

Reference

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