Antidepressant Mechanism and Pharmacodynamic Characteristics of Venlafaxine and Fluxetine Based on Metabolomics

OBJECTIVE To evaluate and compare the antidepressant effects and mechanisms of venlafaxine and fluoxetine by metabolomic approach.METHODS Two positive drugs were employed to intervene the chronic unpredictable mild stress(CUMS) induced rat depression model.The behavioral changes of rats were observed;meanwhile,urine samples were collected and subjected to GC-MS analysis to find potential biomarkers of depression.RESULTS The behavioral data of the drug treatment groups were significantly different(P0.05) with the model group,showing obvious antidepressant effect.Metabolomic analysis showed that venlafaxine group located closer to the healthy controls,showing better antidepressant efficacy than fluoxetine.Fifteen potential biomarkers were identified from the loading plot between control and model group,and more perturbed metabolites were reversed by venlafaxine.CONCLUSION Both drugs have significant antidepressant efficacy,and venlafaxine shows better effect.Metabolomic approach was applied in this study to analyze the regulation of biomarkers and compare the mechanisms of the two drugs.These results provide new methods for the evaluation of drug efficacy.