What is Tesofensine?
Tesofensine is a triple monoamine reuptake inhibitor (TMRI) initially developed for neurodegenerative diseases (e.g., Parkinson’s, Alzheimer’s) but later investigated for its potent effects on weight loss and appetite suppression. It is primarily used in obesity research to reduce body weight, improve metabolic parameters, and enhance energy expenditure. Tesofensine is administered orally as a tablet (e.g., 500 mcg) and has garnered attention for its significant efficacy in weight management, with potential applications in type 2 diabetes and cardiometabolic health.
Mechanism of Action
Tesofensine inhibits the reuptake of dopamine, norepinephrine, and serotonin in the brain by blocking their respective transporters (DAT, NET, SERT). This increases synaptic levels of these monoamines, leading to:
- Appetite Suppression: Enhanced serotonin and norepinephrine signaling reduces hunger and promotes satiety, decreasing caloric intake.
- Increased Energy Expenditure: Dopamine and norepinephrine stimulation boosts resting metabolic rate and thermogenesis, burning more calories.
- Improved Mood and Motivation: Dopamine elevation enhances reward-driven behaviors, supporting adherence to diet and exercise regimens.
- Metabolic Effects: Modulates insulin sensitivity and fat metabolism, contributing to weight loss and glycemic control.
Unlike traditional stimulants (e.g., phentermine), tesofensine’s balanced monoamine inhibition provides robust weight loss with fewer cardiovascular side effects, though it still increases heart rate and blood pressure at higher doses.
Clinical Efficacy and Benefits
Clinical trials have demonstrated that tesofensine is highly effective for weight loss and metabolic improvement in obese individuals, with secondary benefits for glycemic control and cardiometabolic health. Key findings include:
- Weight Loss: Phase II trials (e.g., Astrup et al., 2008) showed dose-dependent weight reductions of 4.5–10.6% (4–12 kg) over 24 weeks at 0.25–1 mg daily, significantly outperforming placebo (2%) and sibutramine (5%). The 0.5 mg dose (equivalent to 500 mcg) achieved ~9% weight loss, with most participants losing ≥5% body weight.
- Appetite Suppression: Reduced hunger scores and increased satiety in subjective assessments, leading to a spontaneous decrease in caloric intake by ~500–800 kcal/day.
- Energy Expenditure: Increased 24-hour energy expenditure by ~6–15% (dose-dependent), enhancing fat oxidation and preventing weight regain.
- Metabolic Benefits: Improved insulin sensitivity, reduced HbA1c (~0.5–1%), and lowered triglycerides in obese patients with prediabetes or type 2 diabetes.
- Cardiometabolic Effects: Decreased waist circumference and visceral fat, reducing cardiovascular risk factors, though blood pressure and heart rate increased slightly (3–5 mmHg, 6–8 bpm).
- Mood Enhancement: Improved mood and quality of life scores, likely due to dopamine-mediated reward effects, supporting long-term adherence.
Who Benefits: Obese individuals (BMI ≥30), those with weight-related comorbidities (e.g., type 2 diabetes, hypertension), or researchers studying appetite regulation and metabolism. Tesofensine is not FDA-approved but is available through compounding pharmacies or research suppliers for investigational use.
Limitations: Benefits are dose-dependent, with 0.5 mg (500 mcg) balancing efficacy and tolerability. Higher doses (1 mg) increase side effects (e.g., insomnia, hypertension) without proportional weight loss gains. Long-term safety data (>1 year) are limited, and discontinuation may lead to partial weight regain without lifestyle changes.
Certificate of Analysis
Tesofensine 500mcg – COA – FYP
| Property | Description |
|---|---|
| Chemical Name | Tesofensine ((1R,2R,3S,5S)-3-(3,4-dichlorophenyl)-2-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane) |
| CAS | 402856-42-2 |
| Molecular Formula | C17H23Cl2NO |
| Molecular Weight | 328.28 g/mol |
| CID | 11370864 |
| Appearance | White Pressed Tablet |
| Purity | ≥98% (verified by HPLC, per USP <621>) |
| Storage | Store at 15–25°C in a dry, sealed container; stable for 24 months |
Learn More About Tesofensine
- “Tesofensine induces dose-dependent body weight loss of up to 10.6% in obese patients” (Astrup et al., Lancet, 2008).
- “Tesofensine: A novel anti-obesity drug with cardiovascular considerations” (Drugs, 2010).
- “Significant weight loss and metabolic benefits observed in Phase II trials” (Obesity Reviews, 2011).
- “Tesofensine’s triple monoamine reuptake inhibition offers a unique approach to appetite control” (Pharmacology & Therapeutics, 2012).
- “Efficacy and safety of tesofensine in obese patients with prediabetes” (Diabetes, Obesity and Metabolism, 2013).
