title: Computational approaches for innovative antiepileptic drug discovery.
abstract: BACKGROUND
  Despite the approval of a large number of antiepileptic agents over the past 25 years, there has been no significant improvement in efficacy of treatments, with one third of patients suffering from intractable epilepsy. This scenario has prompted the search for innovative drug discovery solutions. While network pharmacology and explanations of the drug resistance phenomena have been proposed to drive the search for more efficacious therapeutic solutions, such alternative approaches have not fully taken hold within the antiepileptic drug discovery community so far.
  
  
  METHODS
  Herein, the author discusses the impact that network pharmacology and the current hypotheses of refractory epilepsy and drug repurposing could have if integrated with anti-epileptic computer-aided discovery.
  
  
  CONCLUSIONS
  With many complex diseases, the advancement in the understanding of disorder pathophysiology in addition to the contribution of systems biology have rapidly translated into the discovery of novel drug candidates. However, antiepileptic drug developers have fallen a little behind in this regard, with fewer examples of computer-aided antiepileptic drug design and network-based approximations appearing in scientific literature. New generation single-target agents have so far shown limited success in terms of enhanced efficacy; in contrast, multi-target agents could possibly demonstrate improved safety and efficacy.
authors.affiliation: a Medicinal Chemistry Department of Biological Sciences, Faculty of Exact Sciences , University of La Plata (UNLP) , La Plata , Argentina.
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D017076:Computer-Aided Design; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D058492:Drug Repositioning; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D058990:Molecular Targeted Therapy; D049490:Systems Biology / Q000379:methods
chemical_list: D000927:Anticonvulsants
keywords: Epilepsy; QSAR; drug design; drug repurposing; hybrid molecules; multi-target agents; network pharmacology; phenotypic screening; refractory epilepsy; systems biology