New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity.
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.
Lankau
Hans-Joachim
HJ
Department of Medicinal Chemistry, elbion AG, Meissner Strasse 191, D-01445 Radebeul, Saxony, Germany. hans-joachim.lankau@elbion.de
Unverferth
Klaus
K
Grunwald
Christian
C
Hartenhauer
Helge
H
Heinecke
Kristina
K
Bernöster
Katrin
K
Dost
Rita
R
Egerland
Ute
U
Rundfeldt
Chris
C
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*
D000927:Anticonvulsants; D010069:Oxadiazoles; D005680:gamma-Aminobutyric Acid