Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders
Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders
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DOI：
10.1021/jm800338j
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发表时间：
2008-07-10
影响因子：
7.3
通讯作者：
Liu, Qingyun
中科院分区：
文献类型：
--
作者：
Shi, Zhi-Cai;Devasagayaraj, Arokiasamy;Liu, Qingyun
描述了一类新型外周色氨酸羟化酶（TPH）抑制剂的发现。这类TPH抑制剂在体外生物化学和基于细胞的测定中表现出优异的效力，并且在口服给药后选择性地降低小鼠肠道中的5-羟色胺水平，而不影响脑中的水平。这些TPH 1抑制剂可能为与肾上腺素能系统失调相关的胃肠道疾病提供新的治疗方法，例如化疗诱导的呕吐和肠易激综合征。
The discovery of a novel class of peripheral tryptophan hydroxylase (TPH) inhibitors is described. This class of TPH inhibitors exhibits excellent potency in in vitro biochemical and cell-based assays, and it selectively reduces serotonin levels in the murine intestine after oral administration without affecting levels in the brain. These TPH1 inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome.