Exploring neurokinin-1 receptor antagonism for depression with structurally differentiated inhibitors.

ABSTRACT: The neurokinin-1 receptor (NK1R) has been investigated as a potential target for major depressive disorder owing to its role in stress regulation and neuroinflammation. However, clinical trials of NK1R antagonists have yielded inconsistent results, leaving it unclear whether these outcomes reflect limitations of NK1R as a therapeutic target or shortcomings inherent to the clinical candidates tested. The majority of previously developed NK1R antagonists contain a 3,5-bis-trifluoromethylphenyl moiety, which enhances receptor binding but may also influence drug metabolism, pharmacokinetics or receptor interactions, potentially affecting therapeutic efficacy. Whether structurally distinct NK1R antagonists exhibit different antidepressant potential remains an open question. Here we used computa

SUBMITTER: Yoo H 

PROVIDER: S-EPMC12686497 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature