Tesofensine

Tesofensine (NS-2330) is a triple monoamine reuptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine (DA; IC50=6.5 nM), norepinephrine (NE;IC50=1.7 nM), and serotonin (5-HT;IC50=11 nM), and with potentials as an anti-obesity agent[1]. Tesofensine is a CNS acting anti-obesity agent[2].

Research Areas >> Metabolic Disease

Signaling Pathways >> Neuronal Signaling >> Dopamine Transporter

Signaling Pathways >> Neuronal Signaling >> Serotonin Transporter

DA/NE/5-HT[1]

Tesofensine (a single dose of 0.1-3  mg/kg, s.c.) induces hypophagia in the DIO rat. A single dose of Tesofensine (0. 1-3 mg/kg, s.c.) robustly and dose dependently inhibits food intake in DIO rats over the 12 h nocturnal observation period. Daily administration of a moderate dose of Tesofensine (2.0 mg/kg, s.c.) over 16 days triggers a significant reduction in body weight after 4 days of administration relative to vehicle-treated controls[3]. Animal Model: Diet-induced obesity (DIO) rat[3] Dosage: 0.1-3 mg/kg Administration: Administered subcutaneously (s.c.); a single dose (acute treatment) Result: The threshold dose for inhibition of total food intake was 1.0 mg/kg. The ED50 for inhibition of total food intake in DIO rats was estimated to be 1.3 mg/kg. Animal Model: Diet-induced obesity (DIO) rat[3] Dosage: 2.0 mg/kg Administration: Administered subcutaneously (s.c.) daily for over 16 days (chronic treatment) Result: The average relative decrease in the body weight of tesofensine-treated DIO rats over the entire treatment period was 8.6±1.4%. When comparing to vehicle controls, the relative weight loss with tesofensine was 13.8±1.4%.

[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.