GR 159897 is a potent, selective NK2 receptor antagonist with anxiolytic properties that inhibits the contraction of experimental animals’ tracheal and intestinal smooth muscle. This study evaluated its effects on stress hormones and cytokines in rats under repeated stress.

Methods: Wistar rats underwent water avoidance stress (WAS) and heterotypic stress (HS). Measurements included fecal pellet output, colorectal transit, and plasma levels of CTRH, ACTH, corticosterone (CORT), and cytokines.

Results: Control rats gained weight, while WAS rats lost weight. Stressed rats treated with GR 159897, increased weight significantly. In HS, there was no significant change in the body weight (BW), and the administration of GR 159897 resulted in a noticeable increase in BW. WAS and HS caused an increase in fecal pellet excretion output in animals, and GR159897 significantly reduced the average number of pellets in WAS animals. CRH levels were significantly different in WAS and HS groups compared to controls. GR 159897 reduced CRH in WAS rats. ACTH levels increased in stress-subjected groups, significantly in HS rats, but GR 159897 decreased its concentration in both stress groups. CORT levels indicated significant differences among the control, WAS, and HS groups. GR 159897 reduced CORT levels in WAS+GR group, but not statistically significant to WAS group. GR 159897 significantly reduced elevated IL-6 levels in stressed rats.

Conclusion: The ability of GR 159897 to reduce colorectal contractions, fecal pellet output, stress hormone levels, and proinflammatory cytokines leads us to conclude that NK2 receptor antagonists could help treat conditions like IBS or inflammatory bowel disease.