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ACS Chem Neurosci. 2013 Jan 16;4(1):16-21. doi: 10.1021/cn3001872.

Revisiting serotonin reuptake inhibitors and the therapeutic potential of "uptake-2" in psychiatric disorders.

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  • 1Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States.


Depression is among the most common psychiatric disorders, and in many patients a disorder for which available medications provide suboptimal or no symptom relief. The most commonly prescribed class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), are thought to act by increasing extracellular serotonin in brain by blocking its uptake via the high-affinity serotonin transporter (SERT). However, the relative lack of therapeutic efficacy of SSRIs has brought into question the utility of increasing extracellular serotonin for the treatment of depression. In this Viewpoint, we discuss why increasing extracellular serotonin should not be written off as a therapeutic strategy. We describe how "uptake-2" transporters may explain the relative lack of therapeutic efficacy of SSRIs, as well as why "uptake-2" transporters might be useful therapeutic targets.

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