Modulation of Peripheral Serotonin Levels by Novel Tryptophan Hydroxylase Inhibitors for the Potential Treatment of Functional Gastrointestinal Disorders
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- 作者：Zhi-Cai Shi ; Arokiasamy Devasagayaraj ; Kunjian Gu ; Haihong Jin ; Brett Marinelli ; Lakshman Samala ; Sheldon Scott ; Terry Stouch ; Ashok Tunoori ; Ying Wang ; Yi Zang ; Chengmin Zhang ; S. David Kimball ; Alan
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：July 10, 2008
- 年：2008
- 卷：51
- 期：13
- 页码：3684 - 3687
- 全文大小：416K
- 年卷期：v.51,no.13(July 10, 2008)
- ISSN：1520-4804
文摘
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.