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J Med Chem. 2008 Jul 10;51(13):3684-7. doi: 10.1021/jm800338j. Epub 2008 Jun 17.

Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders.

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  • 1Lexicon Pharmaceuticals, 350 Carter Road, Princeton, New Jersey 08540, USA.


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.

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