Sugar sulfamates for seizure control: discovery and development of topiramate, a structurally unique antiepileptic drug.
TOPAMAX((R)) (topiramate) 1, is a broad-spectrum anticonvulsant that has been marketed worldwide for the treatment of epilepsy and migraine. We discovered this blockbuster drug serendipitously in a project that originally sought a new antidiabetic agent. Topiramate has useful neurological effects that derive from multiple CNS mechanisms of action, but it is basically a "neurostabilizer" by virtue of attenuating the excitability of brain neuronal pathways. During its extensive clinical use, topiramate was also found to possess antimetabolic dysfunction activity, which could be applicable in the treatment of diabetes and obesity. This article discusses research results and events surrounding the discovery and development of topiramate.
Maryanoff
Bruce E
BE
Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA. bmaryano@prdus.jnj.com
D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D005632:Fructose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose