Description

Tesofensine (NS2330 – Monoamine Reuptake Inhibitor)

Tesofensine is a centrally acting monoamine reuptake inhibitor studied for its potential to modulate appetite, energy expenditure, and neurochemical signaling. Originally developed as a treatment for neurodegenerative disorders, Tesofensine has since gained significant interest in obesity and metabolic research due to its ability to promote weight loss by modulating dopaminergic, serotonergic, and noradrenergic neurotransmission.

Tesofensine functions by inhibiting the reuptake of dopamine (DA), serotonin (5-HT), and norepinephrine (NE), leading to increased concentrations of these neurotransmitters in synaptic clefts. This mechanism enhances central satiety signaling and metabolic rate while suppressing appetite. Unlike stimulant-based weight-loss agents, Tesofensine appears to exert thermogenic and appetite-suppressing effects without inducing major cardiovascular stimulation in early models.

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Chemical Makeup

• Chemical Name: (3R)-1-Benzyl-3-(2-(dimethylamino)ethyl)-2,3-dihydro-1H-indol-5-ol hydrochloride

• Molecular Formula: C17H23NO·HCl

• Molecular Weight: 297.83 g/mol

• Form: Lyophilized powder or capsule (for research use only)

• Solubility: Soluble in DMSO and ethanol; limited aqueous solubility

• Stability: Store below −20°C for long-term preservation

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Research & Preclinical Investigations

Appetite Suppression and Weight Reduction

In preclinical models and early-phase clinical trials, Tesofensine significantly reduced caloric intake and body weight in obese subjects by acting on appetite-regulating centers in the hypothalamus. The compound appears to prolong monoamine signaling, enhancing satiety and reducing hunger. Weight loss observed with Tesofensine has outperformed that of certain GLP-1 receptor agonists and placebo in controlled studies.

Neurochemical Modulation

Tesofensine’s mechanism involves simultaneous reuptake inhibition of serotonin, dopamine, and norepinephrine, making it functionally similar to a triple monoamine reuptake inhibitor. This has prompted interest in its application to models of Parkinson’s disease, Alzheimer’s disease, and mood disorders, where deficits in monoaminergic signaling are present.

Energy Expenditure and Thermogenesis

Research has also shown Tesofensine may increase basal metabolic rate (BMR), leading to greater fat oxidation and energy expenditure. These findings suggest Tesofensine’s impact is twofold—reducing energy intake while increasing output, a rare combination among non-stimulant compounds studied in obesity models.

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Research Use Only

Tesofensine is offered strictly for in vitro and in vivo laboratory research. It is not approved for human use, medical treatment, or diagnostic purposes. All research applications must comply with institutional safety standards.

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References

1. Astrup A, et al. Effect of Tesofensine on weight loss in obese patients: a randomized, double-blind, placebo-controlled trial. Lancet. 2008;372(9653):1906–1913.

2. Thomsen WJ, Grottick AJ. Monoamine reuptake inhibitors as novel anti-obesity agents. Curr Top Med Chem. 2010;10(17):1800–1807.

3. Enevoldsen AM, et al. Tesofensine: a triple monoamine reuptake inhibitor for neurodegenerative and metabolic disorders. CNS Drug Rev. 2006;12(1):21–38.