Pharmacodynamic and toxicological evaluation of duloxetine

Aim To evaluate the antidepressant activity and toxicity of duloxetine,a serotonin and noradrenaline reuptake inhibitor.Methods Tail suspension test and forced swimming test in mice were used to evaluate the antidepressant activity of duloxetine,and acute toxicity test in mice and CCK-8 chromatometry were applied to investigate the general toxicity and cytotoxicity of duloxetine.Results In the tail suspension test and forced swimming test in mice,both oral and intraperitoneal administration of duloxetine reduced the immobility time in a dose-dependent manner,without a stimulant effect on the locomotor activity.The medial lethal dose of acute oral or intraperitoneal administration of duloxetine was 177.1 mg·kg-1 and 75.5 mg· kg-1,respectively,and the in vitro IC50 to HepG2 cell was 68.8 μmol·L-1.Conclusion Duloxetine exerted an excellent antidepressant effect,and the acute toxicity response was mainly related to CNS,with potential side effect on the gastrointestinal tract.