title: New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity.
abstract: A series of 3- and 5-aryl-1,2,4-oxadiazole derivatives were prepared and tested for anticonvulsant activity in a variety of models. These 1,2,4-oxadiazoles exhibit considerable activity in both pentylenetetrazole (PTZ) and maximal electroshock seizure (MES) models. Compound 10 was protective in the PTZ model in rats with an oral ED(50) of 25.5mg/kg and in the MES model in rats with an oral ED(50) of 14.6mg/kg. Neurotoxicity (rotarod) was observed with an ED(50) of 335mg/kg. We found several oxadiazoles that acted as selective GABA potentiating compounds with no interaction to the benzodiazepine binding site.
authors.affiliation: Department of Medicinal Chemistry, elbion AG, Meissner Strasse 191, D-01445 Radebeul, Saxony, Germany. hans-joachim.lankau@elbion.de
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lankau
authors.forename: Klaus
authors.initials: K
authors.lastname: Unverferth
authors.forename: Christian
authors.initials: C
authors.lastname: Grunwald
authors.forename: Helge
authors.initials: H
authors.lastname: Hartenhauer
authors.forename: Kristina
authors.initials: K
authors.lastname: Heinecke
authors.forename: Katrin
authors.initials: K
authors.lastname: Bernöster
authors.forename: Rita
authors.initials: R
authors.lastname: Dost
authors.forename: Ute
authors.initials: U
authors.lastname: Egerland
authors.forename: Chris
authors.initials: C
authors.lastname: Rundfeldt
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D010069:Oxadiazoles; D005680:gamma-Aminobutyric Acid