Sibutramine hydrochloride monohydrate is a novel 5-HT (serotonin) and noradrenaline reuptake inhibitor (SNRI). The IC₅₀ for Sibutramine block of voltage-gated K⁺ channel (K_V)4.3 is 17.3 μM. IC50 & Target: 5-HT (serotonin) reuptake^[1]
IC50: 17.3 μM (K_V4.3) ^[2] In Vitro: Sibutramine is a novel 5-HT (serotonin) and noradrenaline reuptake inhibitor (SNRI). Sibutramine reduces the food intake of rodents and this effect is partially or completely reversed by pretreating with 5-HT or noradrenaline antagonists, indicating that both neurotransmitters are involved in sibutramine's hypophagic effect^[1]. Sibutramine causes the concentration-dependent block of the K_V1.3 and K_V3.1 currents with IC₅₀s of 3.7 and 32.7 μM, respectively. The steady-state currents of K_V1.3 and K_V3.1 are decreased by Sibutramine in a concentration-dependent manner with IC₅₀s of 3.7±0.7 (n=6) and 32.7±5.0 μM (n=5), respectively^[2]. In Vivo: Sibutramine (SIB) (5 mg/kg ip), which blocks the reuptake of both 5-hydroxytryptamine (5-HT) and noradrenaline (NA), also requires ARC pro-opiomelanocortin (POMC) neurons to achieve its appetitive effects in male and female mice. Sibutramine (5 mg/kg) suppresses 3-hour dark cycle food intake to a comparable extent in young adult and middle-aged male and female POMC-EGFP mice^[3]. In normal Wistar rats, 3 mg/kg Sibutramine produces a marked (~30%) inhibition of food intake on the first day of dosing. Consistent with published data, the effects of Sibutramine on food intake diminished with time, although cumulative food intake over the 9-day study is significantly (P<0.001) lower in Sibutramine-treated (213.3±5.7 g) than in vehicle-treated (260.2±3.0 g) rats. Sibutramine also significantly reduces overall body weight gain (vehicle 30±2 g, Sibutramine 14±3 g; P<0.001)^[4].