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Metabolic profiling of norepinephrine reuptake inhibitor atomoxetine.


ABSTRACT: Atomoxetine (ATX), a selective and potent inhibitor of the presynaptic norepinephrine transporter, is used mainly to treat attention-deficit hyperactivity disorder. Although multiple adverse effects associated with ATX have been reported including severe liver injuries, the mechanisms of ATX-related toxicity remain largely unknown. Metabolism frequently contributes to adverse effects of a drug through reactive metabolites, and the bioactivation status of ATX is still not investigated yet. Here, we systematically investigated ATX metabolism, bioactivation, species difference in human, mouse, and rat liver microsomes (HLM, MLM, and RLM) and in mice using metabolomic approaches as mice and rats are commonly used animal models for the studies of drug toxicity. We identified thirty one ATX meta

SUBMITTER: MacKenzie KR 

PROVIDER: S-EPMC7506503 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature