Tesofensine 500mcg x 100ct

Compound Name: Tesofensine

Synonyms: NS-2330, 3-[bis(benzyl)methylamino]-2-(ethoxymethyl)-1-(3,4-dichlorophenyl)-tropane

CAS Number: 195875-84-4

Molecular Formula: C₁₇H₂₃Cl₂NO

Molecular Weight: ~328.3 g/mol

Structure: Synthetic triple monoamine reuptake inhibitor

Peptide Sequence: N/A; Not a peptide

Chemical Structure:

Source: PubChem

Mechanism of Action: Tesofensine acts by competitively inhibiting the reuptake of dopamine, norepinephrine, and serotonin in the central nervous system. By blocking their respective transporters, tesofensine prolongs monoamine signaling in key brain regions involved in appetite and energy homeostasis, including the lateral hypothalamus. This results in suppressed food intake, increased satiety, and enhanced energy metabolism. Tesofensine’s unique triple reuptake inhibition differentiates it mechanistically from other anti-obesity agents targeting only one or two neurotransmitter systems^1-4.

Biological Activity: Tesofensine exhibits potent appetite suppressant and weight-reducing effects in animal models and clinical studies. In rodents and humans, tesofensine significantly decreases caloric intake, promotes loss of body fat (especially visceral fat), and improves metabolic profiles (reducing cholesterol, triglycerides, and insulin). It has shown greater efficacy for weight loss than sibutramine and rimonabant in preclinical head-to-head studies. Tesofensine also modulates hypothalamic neuronal activity, specifically silencing GABAergic neurons that stimulate feeding, and augments fat oxidation and night-time energy expenditure. At clinically relevant doses, tesofensine generally produces mild adverse events; however, higher doses can impact heart rate and blood pressure^1-4.

Storage: Store at 2–8°C, protected from light and humidity.

Drug Categories: Anti-obesity agents, Appetite suppressants, Monoamine reuptake inhibitors, Experimental CNS agents

Additional Notes: Tesofensine is not approved for human use outside of a research setting. There are ongoing investigations into its synergistic effects with serotonergic agents to prolong weight loss and potentially prevent weight regain. It has a lower observed potential for abuse compared to classic stimulants and does not typically induce motor stereotypy at therapeutic doses

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

Tesofensine is a novel, small-molecule, synthetic derivative belonging to the phenyltropane class, designed as a potent triple reuptake inhibitor of dopamine, norepinephrine, and serotonin^1,2. Developed originally for neurodegenerative diseases and later repurposed for obesity, tesofensine demonstrated superior efficacy in reducing body weight and adiposity compared to other anti-obesity drugs in both animal models and clinical studies. Its primary action is central. It acts synergistically and enhances monoaminergic signaling at multiple brain sites involved in appetite and energy regulation, with notable efficacy in suppressing caloric intake and sustaining weight loss². Additionally, it modulates metabolic markers such as cholesterol, triglycerides, and plasma insulin, and has been associated with improvements in quality-of-life parameters during clinical trials^1-4. An important aspect of tesofensine’s pharmacology is its low potential for abuse relative to classical stimulants, likely due to its differentiated neurochemical impact and lack of pronounced behavioral stereotypy at therapeutic doses. Its safety profile is favorable at moderate doses, with most adverse effects being mild or transient, such as dry mouth, insomnia, and mild increases in heart rate^3,4.

Research Highlights

• Significantly greater weight loss in obese versus lean animals; superior to sibutramine/rimonabant in animal models^1,3.
• Silences lateral hypothalamic GABAergic neurons-blunting feeding drive and enhancing anorexigenic effect³.
• Does not alter taste or palatability of sweet foods, ruling out aversive mechanisms for appetite suppression³.
• Synergistic with serotonin agents such as 5-HTP to prolong and sustain weight loss, potentially delaying rebound weight gain³.

Mechanism of Action

Dopamine Transporter (DAT) Inhibition

• Inhibits central reuptake of dopamine, increasing extracellular DA in reward and feeding circuits (notably nucleus accumbens and hypothalamus)³.
• Prolonged DA signaling reduces the hedonic drive for food, decreases food reward, and helps modulate motivational aspects of feeding^1,2.
• Unlike typical stimulants, DA transporter occupancy by tesofensine does not trigger significant behavioral stereotypy at therapeutic doses^1-3.

Norepinephrine Transporter (NET) Inhibition

• Blocks norepinephrine reuptake, increasing synaptic NE especially in the hypothalamus and limbic regions¹.
• Enhanced NE signaling increases energy expenditure (thermogenesis), heightens satiety, and further suppresses appetite².
• Inhibition of NE reuptake is key to the compound’s effect in reducing food intake and boosting metabolic rate^1,2.

Serotonin Transporter (SERT) Inhibition

• Blocks serotonin reuptake, raising 5-HT levels, particularly within appetite and satiety centers of the brain (hypothalamus)³.
• Elevated 5-HT signals promote satiety, suppress hunger, and, via downstream signaling, reduce caloric intake³.
• Synergizes with other serotonergic agents (like 5-HTP) to prolong weight loss and decrease risk of rebound³.

Lateral Hypothalamus GABAergic Neuron Silencing

• Inhibits activity of LH GABAergic neurons that normally stimulate feeding behavior³.
• Experimental silencing of these neurons potentiates tesofensine’s anorexigenic effect, highlighting a direct action at neural circuits controlling energy balance³.

Pharmacokinetic Profile

• Route of Administration: Oral (clinical), subcutaneous (preclinical/animal studies)
• Dosing Frequency: Once daily
• Half-Life: Long (t½ up to ~284 hours in humans)

Formulation & Handling

• Supplied as a lyophilized powder or aqueous solution.
• Store at 4°C in a dry, light-protected environment.

Selected Clinical Trial Activity

References

¹Bello, N.T. & Zahner, M.R. Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity. Expert Opin. Investig. Drugs 18, 1717–1726 (2009).

²Appel, L., Bergström, M., Buus Lassen, J. & Långström, B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: Dopamine transporter occupancy as measured by PET. Eur. Neuropsychopharmacol. 24, 251–261 (2014).

³Rascol, O. et al. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch. Neurol. 65, 577–583 (2008).

⁴Perez, C.I. et al. Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons. PLoS ONE 19, e0300544 (2024).