Appearance: Solid powder
Telotristat(cas# 1033805-28-5), also known as LP-778902, is the acid form of Telotristat ethyl, and the active metabolite of LX1606 (Telotristat etiprate), which is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor and serotonin synthesis inhibitor with potential antiserotonergic activity. Blocking peripheral serotonin synthesis by telotristat reduces severity of both chemical- and infection-induced intestinal inflammation.
1. Gut. 2014 Jun;63(6):928-37. doi: 10.1136/gutjnl-2013-304901. Epub 2013 Jun 7.
Pharmacological reduction of mucosal but not neuronal serotonin opposes
inflammation in mouse intestine.
Margolis KG(1), Stevanovic K, Li Z, Yang QM, Oravecz T, Zambrowicz B, Jhaver KG,
Diacou A, Gershon MD.
(1)Department of Pediatrics, Columbia University, College of P&S, , New York, New
Gut. 2014 Jun;63(6):866-7.
OBJECTIVE: Enterochromaffin cell-derived serotonin (5-HT) promotes intestinal
inflammation. We tested hypotheses that peripheral tryptophan hydroxylase (TPH)
inhibitors, administered orally, block 5-HT biosynthesis and deplete 5-HT from
enterochromaffin cells sufficiently to ameliorate intestinal inflammation;
moreover, peripheral TPH inhibitors fail to enter the murine enteric nervous
system (ENS) or central nervous systems and thus do not affect constitutive
DESIGN: Two peripheral TPH inhibitors, LP-920540 and telotristat etiprate
(LX1032; LX1606) were given orally to mice. Effects were measured on 5-HT levels
in the gut, blood and brain, 5-HT immunoreactivity in the ENS, gastrointestinal
motility and severity of trinitrobenzene sulfonic acid (TNBS)-induced colitis.
Quantitation of clinical scores, histological damage and intestinal expression of
inflammation-associated cytokines and chemokines with focused microarrays and
real-time reverse transcriptase PCR were employed to evaluate the severity of
RESULTS: LP-920540 and LX1032 reduced 5-HT significantly in the gut and blood but
not in the brain. Neither LP-920540 nor LX1032 decreased 5-HT immunoreactive
neurons or fibres in the myenteric plexus and neither altered total
gastrointestinal transit time, colonic motility or gastric emptying in mice. In
contrast, oral LP-920540 and LX1032 reduced the severity of TNBS-induced colitis;
the expression of 24% of 84 genes encoding inflammation-related cytokines and
chemokines was lowered at least fourfold and the reduced expression of 17% was
CONCLUSIONS: Observations suggest that that peripheral TPH inhibitors uncouple
the positive linkage of enterochromaffin cell-derived 5-HT to intestinal
inflammation. Because peripheral TPH inhibitors evidently do not enter the murine
ENS, they lack deleterious effects on constitutive intestinal motility in mice.