Network-Pharmacology and Central Nervous System Drug Development

Despite the downward trend in the overall burden of disease and introduction of numerous new medications for brain disorders, the global burden of central nervous system (CNS) conditions has significantly increased in the last few decades. On the other hand, the development of CNS pharmacological treatments presents particularly high attrition rates and long development times. One possible explanation for this phenomenon is the intrinsic complexity of CNS disorders, which makes unmet therapeutic needs for such conditions a “high-hanging fruit.” Network pharmacology has challenged several well-rooted paradigms in the drug discovery field, such as the search for highly selective drugs or the notion that “the most potent the drug candidate, the better.” Multi-target drugs, rationally chosen combination therapies, and low-affinity ligands represent frequent embodiments of the systems pharmacology perspective in the drug discovery field. This chapter reviews some recent applications of this perspective in the field of CNS therapy R&D. The ongoing paradigm change, which has already provided some first-in-class approved medications, may be summarized under the motto “complex diseases require complex therapeutic solutions.”