Audiogenic seizures in DBA/2 mice discriminate sensitively between low efficacy benzodiazepine receptor agonists and inverse agonists.
In experiments with audiogenic seizures in DBA/2 mice, we observed that several socalled benzodiazepine receptor antagonists exhibited either anticonvulsive (Ro 15-1788, PrCC) or proconvulsive (FG 7142, beta-CCE, CGS 8216) effects at high receptor occupancy (17-85%), as compared to benzodiazepines and DMCM which had anticonvulsive and proconvulsive actions, respectively, at very low receptor occupancy (less than 10%). Sensitive distinction between benzodiazepine receptor ligands with low anticonvulsive efficacy (partial agonists) and ligands with low proconvulsive, and maybe anxiogenic, efficacy (partial inverse agonists) can thus be obtained in sound seizure susceptible mice.
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D005442:Flumazenil; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011720:Pyrazoles / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A; D012640:Seizures / Q000503:physiopathology*
D000927:Anticonvulsants; D001570:Benzodiazepinones; D002243:Carbolines; D003292:Convulsants; D011720:Pyrazoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one