The Design, Synthesis and Structure–Activity Relationship of Mixed Serotonin, Norepinephrine and Dopamine Uptake Inhibitors

  • Zhengming ChenEmail author
  • Ji Yang
  • Phil Skolnick
Part of the Topics in Medicinal Chemistry book series (TMC, volume 4)


The evolution of antidepressants over the past four decades has involved the replacement of drugswith a multiplicity of effects (e.g., TCAs) by those with selective actions (i.e., SSRIs). This strategywas employed to reduce the adverse effects of TCAs, largely by eliminating interactions with certain neurotransmittersor receptors. Although these more selective compounds may be better tolerated by patients, selective drugs,specifically SSRIs, are not superior to older drugs in treating depressed patients as measured by responseand remission rates. It may be an advantage to increase synaptic levels of both serotonin and norepinephrine,as in the case of dual uptake inhibitors like duloxetine and venlafaxine. An important recent developmenthas been the emergence of the triple-uptake inhibitors (TUIs/SNDRIs), which inhibit the uptake of the threeneurotransmitters most closely linked to depression: serotonin, norepinephrine, and dopamine. Preclinicalstudies and clinical trials indicate that a drug inhibiting the reuptake of all three of these neurotransmitterscould produce more rapid onset of action and greater efficacy than traditional antidepressants. This reviewwill detail the medicinal chemistry involved in the design, synthesis and discovery of mixed serotonin,norepinephrine and dopamine transporter uptake inhibitors.

Design Monoamine SNDRI Synthesis and SAR Triple-uptake inhibitor  


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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.DOV Pharmaceutical, Inc.SomersetUSA

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