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

摘要: LX-1031 is a heterocyclic substituted phenylalanine analog, an oral small-molecule (molecular weight 538) tryptophan hydroxylase (TPH) inhibitor that reduces synthesis of serotonin (5-HT) peripherally and being developed for conditions characterized by excess 5-HT expression such as diarrhea-predominant irritable bowel syndrome (IBS-D) and, possibly, carcinoid diarrhea. The goal blocking the effects excessive certainly not new (1). However, prior approaches aimed at inhibition 5-HT, with para-chlorophenylalanine, have been impeded central adverse brain consequent affective disorders (2,3). Carcinoid diarrhea principal condition resulting from production usually metastatic tumor in liver; it responds to 5-HT’s octreotide treatment (4,5), or on motor (6) secretory (7,8) mechanisms result alosetron (9). Tryptophan expressed tumors (10) may potentially be target pharmacological this class agent has sufficient systemic exposure; might constitute effective relatively rare disorder compared chronic associated IBS. The objective review appraise pharmacology assess its potential relative medications development IBS. IBS considered disease brain-gut axis. It involve broad range physiological psychological alterations affecting regulation, gut function, visceral perception, mucosal integrity function (11). Published evidence supports role psychosocial (e.g. life event stress) physical (e.g., enteric infections) stressors peripheral triggers, respectively (12), putative low-grade inflammation pathogenesis (12).