Medicinal Chemistry Reviews

Volume 50, Chapter 17
Case History:  Brintellix® (Vortioxetine, LU AA21004), an Antidepressant with Multimodal Activity
Benny Bang-Andersen, Morten Jørgensen, Christoffer Bundgaard, Klaus Gjervig Jensen, and Connie Sanchéz

1.    Introduction                                                                                                                433

2.   Discovery of Vortioxetine                                                                                          434

      2.1        Biological Rationale and Working Hypothesis                                            434

      2.2       Lead Identification and Optimization                                                          435

      2.3       DMPK Properties Including Metabolites of Vortioxetine                           436

      2.4       Synthetic Platform Supporting Lead Optimization and Scale-up of

                  Vortioxetine                                                                                                  439         

3.   Pharmacology of Vortioxetine                                                                           441          

      3.1        Therapeutic targets                                                                                         441

      3.2       Target Engagement—Bridging Preclinical and Clinical Findings               441

      3.3       Vortioxetine’s Proposed Mechanism of Action                                           443

      3.4       Effects of Vortioxetine in Relevant Animal Models                                    444

4.   Clinical Profile of Vortioxetine                                                                                  445

5.   Conclusions                                                                                                                 445

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