title: Anticonvulsant activity of pyrid-3-yl-sulfonyl ureas and thioureas.
abstract: The N-[(4-cycloheptylaminopyrid-3-yl)sulfonyl]-N'-cycloheptyl urea, a neuroprotective agent, and 10 chemically related sulfonyl(thio)ureas were evaluated in the maximal electroshock seizure test in mice. This sulfonylurea, BM 27, and two structurally related sulfonylthioureas, BM 11 and BM 34, emerged with a 50% effective dose (ED50) of 2.87, 1.72, and 1.19 mg/kg, respectively. Their anticonvulsant profiles were found to be similar to that of phenytoin: active in the maximal electroshock seizure (MES) test and inactive in chemically induced seizures (pentetrazole, strychnine, bicuculline, picrotoxine, N-methyl-D,L-aspartic acid). These compounds exhibited a higher protective index and potency than those of phenytoin. Additional work remains necessary, however, to determine whether BM 27 is of clinical interest.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacy, University of Liege, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Masereel
authors.forename: D M
authors.initials: DM
authors.lastname: Lambert
authors.forename: J M
authors.initials: JM
authors.lastname: Dogné
authors.forename: J H
authors.initials: JH
authors.lastname: Poupaert
authors.forename: J
authors.initials: J
authors.lastname: Delarge
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077786:Torsemide
chemical_list: D000927:Anticonvulsants; D004232:Diuretics; D018696:Neuroprotective Agents; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; C104940:BM 11; C104936:BM 27; C104938:BM 34; D013890:Thiourea; D000077786:Torsemide