In vitro, in vivo, and in silico approaches for evaluating the preclinical DMPK profiles of ammoxetine, a novel chiral serotonin and norepinephrine reuptake inhibitor.

ABSTRACT:

Background and aim

Ammoxetine, a novel chiral serotonin and norepinephrine reuptake inhibitor, holds promise for major depressive disorder treatment. This study aimed to thoroughly investigate its preclinical drug metabolism and pharmacokinetics (DMPK) profiles.

Methods

The preclinical DMPK profiles of ammoxetine were examined through in vitro, in vivo, and in silico methods.

Results

Assessment of blood-brain barrier penetration via MDCK-MDR1 cells revealed strong brain permeation by ammoxetine, despite being a probable P-glycoprotein (P-gp) substrate. Molecular docking indicated a robust binding interaction between ammoxetine and P-gp. Ammoxetine was well absorbed orally, with T_max ranging from 0.75 to 3.83 h in rats and 0.75-1.

SUBMITTER: Zhu X 

PROVIDER: S-EPMC11579541 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature