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The therapeutic potential of peripheral 5-HT synthesis inhibitors has been demonstrated in a number of clinical and pre-clinical studies in diseases including carcinoid syndrome, lung fibrosis, ulcerative colitis and obesity. Due to the long half-life of 5-HT in blood and lung, changes in steady-state levels are slow to manifest themselves. Here, the administration of stable isotope labeled tryptophan (heavy \u201ch-Trp\u201d) and resultant<jats:italic>in vivo<\/jats:italic>conversion to h-5-HT is used to monitor 5-HT synthesis in rats. Dose responses for the blockade of h-5-HT appearance in blood with the TPH inhibitors L-<jats:italic>para<\/jats:italic>-chlorophenylalanine (30 and 100\u2009mg\/kg) and telotristat etiprate (6, 20 and 60\u2009mg\/kg), demonstrated that the method enables robust quantification of pharmacodynamic effects on a short time-scale, opening the possibility for rapid screening of TPH1 inhibitors<jats:italic>in vivo<\/jats:italic>. In the bleomycin-induced lung fibrosis rat model, the mechanism of lung 5-HT increase was investigated using a combination of synthesis and steady state 5-HT measurement. Elevated 5-HT synthesis measured in the injured lungs was an early predictor of disease induced increases in total 5-HT.<\/jats:p>","DOI":"10.1038\/srep30059","type":"journal-article","created":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T05:32:56Z","timestamp":1469165576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Serotonin biosynthesis as a predictive marker of serotonin pharmacodynamics and disease-induced dysregulation"],"prefix":"10.1038","volume":"6","author":[{"given":"Richard W. 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