In vivo evaluation of diaminodiphenyls: anticonvulsant agents with minimal acute neurotoxicity.
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.
Worthen
David R
DR
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536-0082, USA.
Bence
Aimee K
AK
Stables
James P
JP
Crooks
Peter A
PA
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
D000814:Aniline Compounds; D000927:Anticonvulsants; D001713:Biphenyl Compounds; C011749:4,4'-thiodianiline