LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin.

ABSTRACT: LX-1031 is an oral, small molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces serotonin (5-HT) synthesis peripherally. It has potential for illnesses characterized by excess 5-HT, such as diarrhea-predominant irritable bowel syndrome (IBS-D) and carcinoid diarrhea. In vitro, inhibition of TPH1 occurred in 10(-8) -10(-7) mol L(-1) range. In vivo in rodents, LX-1031 has no effect on brain 5-HT while dose-dependently reducing 5-HT, particularly in the small bowel. After oral LX1031 in humans, systemic exposure is very low, plasma concentrations are linear in dose range 250-750 mg q.i.d.; the median T(1/2) for elimination is ∼ 20 h, and repeat administration for 14 days doubles C(max) . In ascending-single-dose and multiple-dose (14 days) trials in healthy volunteers, LX-1031, 2-4 g

SUBMITTER: Camilleri M 

PROVIDER: S-EPMC3076306 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature