Biological Activity
Telotristat etiprate (LX1606 Hippurate) is a novel, orally-delivered inhibitor of tryptophan hydroxylase that reduces serotonin production.
In Vitro
No in vitro data are provided in the current product source. Contact us for further information.
In Vivo
Telotristat ethyl (15, 50, 150, 300 mg/kg, po, qd) reduces serotonin content in the periphery, but not in the brain of the mice. Telotristat ethyl (200 mg/kg po, qd) prevents the increase in blood neutrophil counts that is observed after TNBS challenge, provides significant protection in a mouse model of inflammatory bowel disease. Telotristat ethyl (200 mg/kg po, qd) protects the mouse IBD model confirmed by histopathology evaluation[1]. Telotristat ethyl (15, 50, 150, 300 mg/kg) depletes 5-HT from the jejunum but not the brain. But Telotristat ethyl (200 mg/kg, p.o.) does not deplete enteric neuronal serotonin (5-HT), or alter constitutive gastrointestinal motility in mice. Telotristat ethyl (200 mg/kg) alleviates the severity of trinitrobenzene sulfonic acid (TNBS)-induced colitis[2].
Animal Administration
For studies of the effects of peripheral TPH inhibitors on gut and brain 5-HT concentrations, LP-920540 is formulated in 0.1% Tween 80 in 0.25% methylcellulose and administered to mice once daily via oral gavage at 10 mL/kg for 4 consecutive days. Telotristat ethyl is formulated in 15% cyclodextrin (CaptisolTM, pH 3-4) or 0.25% methylcellulose and given to mice once daily via oral gavage at 10 mL/kg for 4 consecutive days. Whole brain, jejunum and colon (mesentery fat removed, gut lumen opened and blotted dry) are collected, snap frozen, and stored at -80ºC for future. LP-920540, Telotristat ethyl, LP-778914, LP-778920 and vehicle control are also formulated with 0.5% methycellulose at appropriate doses in coded vials. The contents of the coded vials are given by oral gavage in amounts determined by the weights of the recipient mice. After the experiments, results are analyzed.
References & source
[1]. Tamas Oravecz, et al. LX1606 (aka LX1032), a Novel Inhibitor of Serotonin Synthesis, Alleviates Development of Inflammatory Bowel Disease in a Preclinical Model.
[2]. Margolis, K.G., et al., Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut, 2013.
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
