Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening

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• 作者：Jeffery N. Talbot ; PhD^a ; ^{jtalbot@roseman.edu} ; Laura M. Geffert ; MS^b ; Jessica E. Jorvig ; MS^a ; Ruben I. Goldstein^a ; Cienna L. Nielsen ; MS^c ; Nicholas E. Wolters ; PharmD^d ; Mary Ellen Amos^d ; Caitlin A. Munro^d ; Elizabeth Dallman^d ; Maddalena Mereu ; PhD^e ; Gianluigi Tanda ; PhD^e ; Jonathan L. Katz ; PhD^e ; Martí ; n Indarte ; PhD^f ; Jeffry D. Madura ; PhD^g ; Hailey Choi ; BS ; PharmD^b ; Rehana K. Leak ; PhD^b ; Christopher K. Surratt ; PhD^b ; ^{surratt@duq.edu}
• 关键词：MAT ; monoamine transporters ; DA ; dopamine ; DAT ; dopamine transporter ; SERT ; serotonin transporter ; NET ; norepinephrine transporter ; SSRI ; serotonin selective reuptake inhibitor ; TCA ; tricyclic antidepressant ; NMDA ; n-methyl-d-aspartate ; TST ; tail suspension test ; FST ; forced swim test ; CPP ; conditioned place preference ; HPLC ; high-performance liquid chromatography ; VS ; virtual screening
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2016
• 出版时间：November-December 2016
• 年：2016
• 卷：150-151
• 期：Complete
• 页码：22-30
• 全文大小：1494 K
• 卷排序：150

文摘

In silico screening identified Ro-25-6981 (coded “MI-4”) as a dopamine transporter ligand. The NMDA receptor antagonist Ro-25-6981 also inhibits monoamine transporters (MATs). Ro-25-6981 exhibits rapid and sustained antidepressant-like effects in animal models. MAT virtual screening is a viable method to identify antidepressant lead compounds. Dual monoaminergic/glutamatergic agents are a novel strategy to treat depression.