title: Exploring the latest avenues for antiepileptic drug discovery and development.
abstract: BACKGROUND
  In about 30% of patients with epilepsy, seizures are not sufficiently controlled with the available antiepileptic medication. There is a need for newer drugs, not only aimed at suppressing seizure activity but for the efficient inhibition of epileptogenesis.
  
  
  METHODS
  In this review, the authors consider different approaches for the management of drug-resistant epilepsy and various possible ways on how to stop epileptogenesis.
  
  
  CONCLUSIONS
  There is limited evidence for antiepileptogenic effects of antiepileptic drugs. Post-status epilepticus animal models will probably help the discovery of antiepileptogenic compounds among already approved non-antiepileptic drugs or other agents. A good example is losartan, which significantly inhibits epileptogenesis in vivo. Some agents that affect the mTOR signaling system, or that inhibit the synthesis of the proconvulsant cytokine as well as those derived from plants (resveratrol) also seem effective in this regard. Furthermore, agonists of peroxisome proliferator-activated receptors have proven effective in some models of seizures but data on their possible antiepileptogenic activity is quite limited. In addition to the discovery of new antiepileptogenic and/or antiepileptic compounds, there is a possibility of improving the treatment of drug-resistant cases through the rational use of antiepileptic drug combinations.
authors.affiliation: a Department of Physiopathology , Institute of Rural Health , Lublin , Poland.|b Department of Pathophysiology , Medical University of Lublin , Lublin , Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Łukawski
authors.affiliation: b Department of Pathophysiology , Medical University of Lublin , Lublin , Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Gryta
authors.affiliation: b Department of Pathophysiology , Medical University of Lublin , Lublin , Poland.|c Isobolographic Analysis Laboratory , Institute of Rural Health , Lublin , Poland.
authors.forename: Jarogniew
authors.initials: J
authors.lastname: Łuszczki
authors.affiliation: a Department of Physiopathology , Institute of Rural Health , Lublin , Poland.|b Department of Pathophysiology , Medical University of Lublin , Lublin , Poland.
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists
chemical_list: D000927:Anticonvulsants; D047492:Peroxisome Proliferator-Activated Receptors
keywords: Antiepileptic drugs; epileptogenesis; losartan; rapamycin; resveratrol; seizures