The discovery of triple reuptake inhibitors (TRIs) for the treatment of depression Shuang Liu,1 Kassoum Nacro,1  Min Hu,1  Ulhas Bhatt,1 Kristen Ryans,1 Aruna Sambandam,1 Wenge Cui,1 Peter R. Guzzo, 1 Bruce J. Sargent,1 Bruce F. Molino 1 Richard E. Olson,2 Dalton King, 2 Yu-Wen Li, 2 Joseph Raybon,2 Wendy Clarke,2 Kim Johnson, 2 Michael Sinz,2 Stephen Adams,2 Nicholas Lodge,2 Thaddeus Molski 2, Snjezana Lelas,2   Divyakant Desai,2  Robert Risinger,2  Ming Zheng, 2 John Houston, 2 Robert Zaczek,2 John E. Macor2   (1) AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212 (2) Bristol Myers Squibb R&D, 5 Research Parkway, Wallingford, CT 06492-7660 Major depressive disorder (MDD) remains an inadequately treated disease in spite of the advances of past decades.  Clinical evidence based on combination studies suggests that adding dopamine transporter inhibition can potentially augment the efficacy of selective serotonin and serotonin/norepinephrine reuptake inhibitors (SSRIs and SNRIs).  Hence, triple reuptake inhibitors (TRIs) that appropriately block DAT, NET and SERT function hold promise as new antidepressant therapies.  BMS-820836 is a novel triple uptake inhibitor that was advanced to Phase II clinical trials.  The design, synthesis, pre-clinical pharmacology and Phase I biomarker results (PET) for BMS-820836 will be presented.  TRIs from related series with different triple inhibition profiles will also be described.

Discovery of triple reuptake inhibitors (TRIs) for the treatment of depression

248th National Meeting (2014)

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