**Background**
Obesity is a complex, chronic disease characterized by excessive adipose tissue accumulation, which significantly increases the risk of cardiovascular diseases, type 2 diabetes, and metabolic syndrome. The management of obesity often requires pharmacological interventions that target the central nervous system (CNS) to regulate appetite and energy expenditure. Monoamine neurotransmitters, including dopamine, norepinephrine, and serotonin, play critical roles in the modulation of food intake and satiety. Consequently, agents capable of modulating the synaptic levels of these neurotransmitters have become primary targets for the development of anti-obesity therapies. In this context, we will introduce a CNS-acting anti-obesity agent – Tesofensine.
**Definition**
Tesofensine (NS-2330) is a potent triple monoamine reuptake inhibitor that induces inhibition of the re-uptake process in the synaptic cleft for dopamine (IC50 = 6.5 nM), norepinephrine (IC50 = 1.7 nM), and serotonin (IC50 = 11 nM).
**In Vivo Studies**
According to the Tesofensine biological activity reported in literature, this compound demonstrates significant appetite-suppressing effects. In vivo studies using diet-induced obesity (DIO) rats showed that a single subcutaneous (s.c.) dose of Tesofensine (0.1-3 mg/kg) robustly and dose-dependently inhibits food intake over a 12-hour nocturnal observation period. The threshold dose for the inhibition of total food intake was found to be 1.0 mg/kg, with an estimated ED50 of 1.3 mg/kg. Furthermore, the Tesofensine protocol for chronic treatment involved daily subcutaneous administration of a moderate dose (2.0 mg/kg) over 16 days. This regimen triggered a significant reduction in body weight starting after 4 days of administration relative to vehicle-treated controls. Over the entire treatment period, the average relative decrease in body weight of treated DIO rats was 8.6±1.4%, representing a relative weight loss of 13.8±1.4% compared to the control group. In conclusion, Tesofensine is a potent triple monoamine reuptake inhibitor that effectively induces hypophagia and weight loss in obese animal models.
Keywords
Tesofensine, 195875-84-4, NS-2330, NS2330, NS 2330, Dopamine Transporter, Serotonin Transporter, DAT, SLC6A3, 5-HTT, SERT, SLC6A4, triple monoamine reuptake, neurotransmitters dopamine, norepinephrine, serotonin, anti-obesity agent, Inhibitor, inhibitor, inhibit
References
[1] Lieuwe Appel, et al. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014 Feb;24(2):251-61.
[2] Ann A Coulter, et al. Centrally Acting Agents for Obesity: Past, Present, and Future. Drugs. 2018 Jul;78(11):1113-1132.
[3] Anne Marie D Axel, et al. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat.Neuropsychopharmacology. 2010 Jun;35(7):1464-76.