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Overview
What is Tesofensine?
Tesofensine (NS2330) is a triple monoamine reuptake inhibitor that blocks the reuptake of dopamine, norepinephrine, and serotonin. Originally developed for Parkinson's and Alzheimer's disease, it demonstrated significant weight loss effects in early trials, leading to its development as an anti-obesity agent. Phase 2 and 3 clinical trials have shown weight loss of 10-12% over 24 weeks, making it one of the more effective investigational weight loss compounds. It works primarily by suppressing appetite and increasing energy expenditure through central nervous system mechanisms.
Key Benefits
Potent appetite suppression with significant weight loss (9-12% over 24 weeks). Once-daily oral dosing with long half-life (~9 days). May also increase resting energy expenditure. Different mechanism than GLP-1 agonists offers alternative approach.
Mechanism of Action
Tesofensine is a triple monoamine reuptake inhibitor that blocks reuptake of dopamine (IC50: 6.5nM), norepinephrine (IC50: 1.7nM), and serotonin (IC50: 11nM). This increases neurotransmitter levels in the hypothalamus and other brain regions controlling appetite and satiety. Recent research shows it silences GABAergic neurons in the lateral hypothalamus that normally promote feeding behavior.
Pharmacokinetics
Research Indications
Significant Weight Reduction
Phase 2/3 trials demonstrate 9-12% body weight loss over 24 weeks, among the highest for investigational obesity drugs
Appetite Suppression
Reduces hunger signals and increases satiety through central nervous system monoamine modulation
Potential Metabolic Benefits
Clinical trials showed improvements in triglycerides, VLDL cholesterol, and insulin levels
Visceral Fat Reduction
Phase 3 data showed significant reduction in visceral fat, the metabolically harmful fat around organs
Research Protocols
Disclaimer
These are commonly discussed research protocols and not medical advice. Consult a healthcare provider before use.
Timing
Take in the morning to minimize insomnia risk. The long half-life (~9 days) means consistent daily dosing is less critical than with shorter-acting medications, but morning dosing is still recommended.
Peptide Interactions
How to Reconstitute
Important
Always use bacteriostatic water (BAC). Sterile technique is essential.
Take one capsule in the morning with or without food
Swallow whole with water
Take at the same time each day for consistent blood levels
Due to long half-life (~9 days), steady state reached after several weeks
Do not take in the evening due to potential insomnia
Quality Indicators
Not FDA Approved
Tesofensine is investigational and not approved for obesity treatment in the US
Compounded Products
Currently only available through compounding pharmacies - quality varies
Third-Party Testing
Verify purity through independent certificate of analysis (COA)
Proper Dosing
Capsules should be accurately dosed at 0.25mg or 0.5mg increments
Unknown Sources
Avoid products without verifiable testing or from unregulated sources
Combination Products
Be cautious of pre-mixed combinations without clinical safety data
What to Expect
- Week 1-2: Noticeable appetite reduction, possible dry mouth and mild insomnia
- Week 2-4: Initial weight loss begins (1-2kg typical)
- Month 1-3: Significant weight loss accumulates (5-8% body weight)
- Month 3-6: Continued weight loss reaching 10-12% in responders
- Long half-life (~9 days) means steady levels without peaks/troughs
- Effects persist for weeks after discontinuation due to long half-life
Side Effects & Safety
- NOT FDA approved - investigational compound only
- May increase heart rate by 5-8 bpm (dose-dependent)
- Can modestly increase blood pressure (1-3 mmHg typical)
- Contraindicated with MAOIs, SSRIs, SNRIs, and stimulants
- Not recommended for those with cardiovascular disease or uncontrolled hypertension
- May cause insomnia - take in the morning only
- Psychiatric effects possible - avoid with depression/anxiety history
- Long half-life means side effects persist if they occur
- Regular cardiovascular monitoring recommended
References
TIPO-1 Phase IIB Trial (2008)
Landmark randomized, double-blind, placebo-controlled trial demonstrating dose-dependent weight loss. The 0.5mg dose showed 9.2% weight loss, approximately double that of FDA-approved obesity medications at the time.
View Study (opens in new tab) →TIPO-4 Extension Trial (48 weeks)
Open-label extension study showing sustained weight loss over 48 weeks of treatment, with participants maintaining 13-14kg weight reduction.
Viking Phase 3 Trial (2018)
Phase 3 registration trial meeting primary and secondary endpoints. Demonstrated significant reductions in waist circumference, body fat, visceral fat, triglycerides, and insulin levels.
View Study (opens in new tab) →Quick Start Guide
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Community Insights
Self-reported by PepPedia users. Not clinical evidence. Health changes reflect all users, including those taking multiple compounds.
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