Sibutramine hydrochloride_product_DataBase

Bioactivity

Sibutramine hydrochloride is a novel 5-HT (serotonin) and noradrenaline reuptake inhibitor (SNRI). The IC50 for Sibutramine block of voltage-gated K+ channel (KV)4.3 is 17.3 μM.

Target

5-HT (serotonin) reuptakeIC50: 17.3 μM (KV4.3)

Invitro

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 KV1.3 and KV3.1 currents with IC50s of 3.7 and 32.7 μM, respectively. The steady-state currents of KV1.3 and KV3.1 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].

Name

Sibutramine hydrochloride

CAS

84485-00-7

Formula

C17H27Cl2N

Molar Mass

316.31

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Heal DJ, et al. Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine. Int J Obes Relat Metab Disord. 1998 Aug;22 Suppl 1:S18-28; discussion S29. [2]. Kim SE, et al. Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, KV1.3 and KV3.1, bySibutramine. J Pharmacol Exp Ther. 2007 May;321(2):753-62. [3]. Burke LK, et al. 5-HT obesity medication efficacy via POMC activation is maintained during aging. Endocrinology. 2014 Oct;155(10):3732-8. [4]. Turnbull AV, et al. Selective antagonism of the NPY Y5 receptor does not have a major effect on feeding in rats. Diabetes. 2002 Aug;51(8):2441-9.

PeptideDB

Sibutramine hydrochloride

CAS: 84485-00-7 F: C17H27Cl2N W: 316.31