Drug Discovery in Epilepsy: A Synthetic Review

Although recurrent unprovoked seizures or epilepsy has been known for more than three thousand years, and even considering pivotal contributions like that of Hypocrates (circa 400 BC) establishing epilepsy as a brain disease instead of a religious or evil phenomenon, it was not until the 20th century that the first relatively effective antiepileptic drugs were discovered. Starting from phenobarbital and phenytoin almost 100 years ago, much research has been devoted to the development of new, more active drugs to treat such a broad category of symptom complexes (Krasowski, 2010). A chronological overview of the aforementioned development would provide interesting information about trial and errors in antiepileptic therapy, but from a chemical point of view (drug discovery) a classification according to structure is by far more useful. That is the aim of this review, thus covering the most relevant literature concerning synthetic approaches to the main anticonvulsant drugs. More detailed, comprehensive reviews on some of the main antiepileptic drugs (AEDs) have been reported so far (Carril et al., 2007; Kraus et al., 2010), in some cases describing also aspects like pharmacokinetics, medicinal uses, approval for commercialization, etc. The present review intends to give a concise outlook at the most significant strategies employed in the synthesis of a good number of AEDs. Currently marketed drugs and some others in development will be briefly examined. Finally, a slightly more profound coverage has been given to some sections (i.e. carbamazepine, oxcarbazepine and eslicarbazepine acetate) on the basis of the relevance, therapeutic importance or promising applications of some AEDs over other ones occasionally employed or with a narrower application spectrum.