title: In vivo evaluation of diaminodiphenyls: anticonvulsant agents with minimal acute neurotoxicity.
abstract: Several diaminodiphenyl analogs were assessed in vivo for their capacity to inhibit seizure induction and propagation in rodents. Both 3,4'- and 4,4'-diaminodiphenyl compounds prevented seizures for as long as 4h after maximal electric shock induction. 4,4'-Diphenyl compounds bridged by a methylene, sulfide, or carbonyl linker also attenuated focal seizure acquisition in a kindling model. Of these analogs, based upon data generated in two rodent species, 4,4'-thiodianiline (1) was identified as the most active compound, significantly reducing seizure staging scores and after-discharge duration for several hours after systemic administration. All compounds were devoid of acute in vivo neurotoxicity at doses well above those required for anticonvulsant activity.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536-0082, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Worthen
authors.forename: Aimee K
authors.initials: AK
authors.lastname: Bence
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000814:Aniline Compounds; D000927:Anticonvulsants; D001713:Biphenyl Compounds; C011749:4,4'-thiodianiline