title: Simple N,N-dimethyl phenylsulfonamides show potent anticonvulsant effect in two standard epilepsy models.
abstract: Optimization of the previously reported benzothiazine analogue A led to the identification of compound 1, which showed anti-convulsant activity in two golden standard animal models of seizure, the MES and scPTZ models. Structure-activity relationship investigation of compound 1 revealed compounds 2, 6 and 19 as attractive anti-epileptic drug (AED) candidates with potent anticonvulsant effect in both the MES and scPTZ models. As these compounds are structurally different from existing AEDs, determination of their mechanism of actions could provide clues to understanding current therapy-resistant seizures. Moreover, these simple phenylsulfoneamide compounds could be good starting points for searching broad spectrum AEDs by such in vivo screening.
authors.affiliation: Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: tomoyuki-1-tanaka@ds-pharma.co.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Yajima
authors.affiliation: Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kiyoshi
authors.affiliation: Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Drug Research Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Iwama
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D015394:Molecular Structure; D010433:Pentylenetetrazole; D051381:Rats; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D013449:Sulfonamides; D010433:Pentylenetetrazole
keywords: Epilepsy; In vivo screening; MES; PTZ; Phenylsulfoneamide