title: Revisiting serotonin reuptake inhibitors and the therapeutic potential of "uptake-2" in psychiatric disorders.
abstract: 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.
authors: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States. daws@uthscsa.edu
authors: Lynette C
authors: LC
authors: Daws
authors: Wouter
authors: W
authors: Koek
authors: Nathan C
authors: NC
authors: Mitchell
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D027701:Organic Cation Transport Proteins / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D027701:Organic Cation Transport Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human