Network pharmacology for antiepileptogenesis: Tolerability of multitargeted drug combinations in nonepileptic vs. post-status epilepticus mice

Highlights • Prevention of epilepsy in patients at risk is a major unmet clinical need. • Epilepsy is a network phenomenon, so that a single drug can probably not halt epileptogenesis. • Combinations of multitargeted drugs may be more effective, but have not been tested as yet. • An algorithm for te...

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Veröffentlicht in:	Epilepsy research 2015-12, Vol.118, p.34-48
Hauptverfasser:	Klee, Rebecca, Töllner, Kathrin, Rankovic, Vladan, Römermann, Kerstin, Schidlitzki, Alina, Bankstahl, Marion, Löscher, Wolfgang
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anticonvulsants - therapeutic use Antiepileptic drugs Blood–brain barrier Disease Models, Animal Drug adverse effects Drug Therapy, Combination - methods Epilepsy Excitatory Amino Acid Agonists - toxicity Female Inflammation Kainic Acid - toxicity Male Mice Muscarinic Agonists - toxicity Neurology Pilocarpine - toxicity Sex Factors Status Epilepticus - chemically induced Status Epilepticus - drug therapy Time Factors
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Zusammenfassung:	Highlights • Prevention of epilepsy in patients at risk is a major unmet clinical need. • Epilepsy is a network phenomenon, so that a single drug can probably not halt epileptogenesis. • Combinations of multitargeted drugs may be more effective, but have not been tested as yet. • An algorithm for testing drug combinations in naive and post-status epilepticus rodents is presented. • As a first step, tolerability of rationally chosen drug combinations was evaluated in mice.
ISSN:	0920-1211 1872-6844
DOI:	10.1016/j.eplepsyres.2015.11.003