ROS-Scavenging Selenofluoxetine Derivatives Inhibit In Vivo Serotonin Reuptake

While the neurochemistry that underpins the behavioral phenotypes of depression is the subject of many studies, oxidative stress caused by the inflammation comorbid with depression has not adequately been addressed. In this study, we described novel antidepressant–antioxidant agents consisting of selenium-modified fluoxetine derivatives to simultaneously target serotonin reuptake (antidepressant action) and oxidative stress. Excitingly, we show that one of these agents (1-F) carries the ability to inhibit serotonin reuptake in vivo in mice. We therefore present a frontier dual strategy that paves the way for the future of antidepressant therapies.