The dysfunction of the peripheral serotonin (5-hydroxytryptamine, 5-HT) system is involved in many diseases, such as carcinoid syndrome, fibrotic disease, atherosclerosis, and pulmonary arterial hypertension. Tryptophan hydroxylase 1 (TPH1) is an aromatic amino acid hydroxylase essential for the biosynthesis of peripheral 5-HT. Telotristat etiprate is the ester prodrug of a potent TPH1 inhibitor, LX-1033, with an IC50 value of 16nM[2]. Telotristat (also known as LP778902) is the active moiety of telotristat etiprate. In C57BL/6 mice, telotristat (~100 mg/kg) supplementation significantly reduced maternal serum serotonin concentration compared with the control dams on day 1 and day 21 of lactation, but did not change serum serotonin level in their pups. Maternal supplementation with telotristat did not significantly alter the ratio of maternal femoral trabecular bone volume to tissue volume. Pups of the dams treated with telotristat showed a reduced ratio of bone volume to tissue volume on the day of weaning, fewer and thinner trabeculae, and increased trabecular spacing compared with control pups. Pups born to telotristat-supplemented dams also had reduced total serum calcium on day 21 of lactation[3].
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